Infections
|
April 24, 2025

Lyme Disease Tests: Timing, Types, and What Results Mean

Medically Reviewed by
Updated On
April 30, 2025

You’ve been outdoors—maybe hiking, gardening, or playing with your kids—and now you're feeling off. Fatigue, joint aches, perhaps even a strange rash. Could it be Lyme disease? You’re not alone in wondering.

Lyme disease (Lyme borreliosis), is the most commonly transmitted tick-borne infection in the United States and among the most frequently diagnosed tick-borne infections worldwide. This guide breaks down Lyme disease testing: when to do it, how it works, and how to understand the results.

[signup]

What Is a Lyme Disease Test?

Before discussing when to test or which test to choose, it’s important to understand what a Lyme disease test is and what it’s actually looking for.

Definition and Testing Purpose

Lyme disease is a tick-borne illness caused by the Borrelia burgdorferi bacteria. It is transmitted through the bite of infected ticks and can affect the skin, joints, nervous system, and heart. Early treatment helps prevent serious complications, but testing can be tricky, especially if symptoms are delayed or vague.

A Lyme disease test looks for signs that your immune system has responded to infection with Borrelia burgdorferi, the bacteria that causes Lyme disease. The most common tests detect antibodies—proteins your body produces to fight off the bacteria. 

In certain situations—particularly when someone has neurological symptoms such as facial paralysis, memory issues, or unexplained tingling—a provider may order a spinal tap to check for Borrelia DNA or antibodies in the cerebrospinal fluid. This can help diagnose cases where the bacteria have affected the brain or spinal cord, known as neuroborreliosis.

Why Testing Matters

Testing is essential in guiding diagnosis and treatment—especially when symptoms are nonspecific and overlap with other illnesses. A reliable test result can help confirm that Lyme disease is the cause of symptoms, support decisions about antibiotic therapy, and rule out other conditions such as viral infections, autoimmune disorders, or fibromyalgia.

The timing of testing is critical: 

  • If the test is done too early—within the first few days of infection—your body may not have produced enough antibodies to be detected. This can result in a false negative, where the test says you’re not infected when you actually are. 
  • On the other hand, if you test months or even years after infection, your body may still show a positive result, even though the bacteria are no longer active. This is because antibodies can persist in the bloodstream long after the infection has been treated successfully.

In addition, not all people with Lyme disease produce measurable antibodies, and some tests may react to other conditions, leading to false positives. That’s why a healthcare provider should always interpret test results alongside your symptoms, physical exam findings, and history of potential tick exposure.

Types of Lyme Disease Tests

Different tests serve different purposes, from screening for early infection to confirming long-term complications.

Two-Tier Antibody Testing (Gold Standard)

This two-step approach is the standard testing method recommended by the CDC and FDA.

  • First Tier: ELISA (Enzyme-Linked Immunosorbent Assay) - This initial blood test checks for IgM (early) and IgG (later) antibodies. If the result is positive or borderline, a second test is done.
  • Second Tier: Western Blot or Second EIA - Confirms antibody presence and can help identify the stage of infection. 

Direct Diagnostic Tests

These look for actual bacterial material rather than antibodies.

  • Polymerase Chain Reaction (PCR) Testing Detects Borrelia DNA, mainly in cerebrospinal fluid or joint fluid. It is useful when Lyme affects the nervous system or joints.
  • Culture and Antigen Detection - Still experimental and not widely used. These methods try to grow or detect parts of the bacteria directly.

At-Home Tests

At-home Lyme disease test kits are available online and at some pharmacies. These kits typically require you to collect a small blood sample through a finger prick, which you then mail to a lab for analysis. Some tests look for antibodies, while others claim to detect bacterial DNA.

While at-home testing offers convenience and privacy, it comes with limitations. The accuracy and quality of these tests can vary, and not all tests are FDA-reviewed. Some may produce false positives or negatives, especially if used too early or late during illness.

Follow up with a healthcare provider if you receive a positive or unclear result. They can confirm the diagnosis with validated laboratory testing and help determine the appropriate next steps in your care.

When Should You Get Tested?

Timing affects test reliability, and symptoms evolve in stages. Knowing when and why to test can prevent missed or incorrect diagnoses.

Symptom Timeline and Risk Exposure

If you've had symptoms for less than 30 days, antibody levels may be too low to detect.
If you have a bull’s-eye rash (erythema migrans), your doctor may diagnose Lyme disease clinically without a test.

Stages of Lyme Disease and Testing Accuracy

Lyme disease is divided into three stages (early localized, early disseminated, and late).  As the disease progresses, test sensitivity improves.

Early Localized Stage (1–4 weeks) 

  • Patients may have a rash, fever, or fatigue. 
  • Tests are often negative at this stage, but treatment may still be started based on symptoms.

Early Disseminated Stage (1–4 months)

  • Bacteria may spread to the heart, joints, or nervous system. 
  • Antibodies are more likely to be detected during this stage.

Late Lyme Disease (Months to Years)

  • Arthritis or neurologic symptoms may appear. 
  • Testing is more accurate, but symptoms can resemble other diseases.

Understanding Test Results

Understanding what Lyme disease test results show and when to follow up is key to getting the proper care.

Negative Test Doesn’t Always Mean No Disease

A negative test result may be reassuring but does not definitively exclude Lyme disease. 

  • If testing is performed too early—typically within the first few weeks of infection—the body may not have produced enough antibodies to be detected. For this reason, false negatives are more common during the early localized stage of the disease.
  • If symptoms such as fever, fatigue, or the characteristic erythema migrans (bull’s-eye rash) persist, retesting after 3 to 4 weeks may be appropriate. 

Additionally, some individuals may never produce measurable antibodies, a condition called seronegative Lyme disease.

Positive Test Doesn’t Always Mean Active Infection

Antibodies can remain in the bloodstream for months or years after recovery. A positive test may reflect past—not current—illness.

A positive test result indicates that the immune system has responded to the Borrelia burgdorferi bacteria. However, this does not always reflect an active infection. Immunoglobulin G (IgG) antibodies can persist in the bloodstream for many months—or even years—after successful treatment, which may lead to confusion when evaluating lingering symptoms.

To determine the clinical significance of a positive test, healthcare providers must consider the full context, including the patient's symptom profile, potential exposure to ticks, and timing of testing relative to symptom onset.

False Positives and Other Conditions

Lyme disease tests aren’t perfect. In some cases, the immune system may produce antibodies that cross-react with other infections or autoimmune conditions, such as:

This cross-reactivity can lead to a false positive result, where the test shows Lyme disease when it’s actually another condition. 

Co-Infections and Complications

Ticks that carry Borrelia burgdorferi can also transmit other pathogens. These co-infections can complicate both diagnosis and treatment. 

Common Tick-Borne Co-Infections

Ticks can transmit multiple organisms during a single bite. These additional infections may present with overlapping symptoms or may not respond to standard Lyme disease treatment alone.

Common co-infections include:

  • Anaplasmosis (Anaplasma phagocytophilum): Causes flu-like symptoms, low white blood cell counts, and elevated liver enzymes.
  • Babesiosis (Babesia microti): A parasitic infection of red blood cells, often presenting with fever, chills, and fatigue. Severe cases can resemble malaria.
  • Powassan Virus: A rare but serious viral infection that can lead to encephalitis (brain inflammation). Symptoms may include headache, confusion, seizures, and, in some cases, long-term neurological impairment.
  • Ehrlichiosis (Ehrlichia chaffeensis): Similar to anaplasmosis but more common in the southeastern and south-central U.S.
  • Bartonellosis (Bartonella spp.): Some evidence suggests possible co-transmission, though more research is needed to confirm its role in tick-borne disease.

These co-infections can intensify the clinical presentation and may require different or additional treatments beyond standard Lyme disease protocols.

When to Suspect Co-Infections

Co-infections should be suspected when symptoms are more severe than expected, when symptoms persist despite appropriate Lyme disease treatment, or when the clinical picture includes features not typically associated with Lyme disease alone.

Examples of red flags that may suggest co-infection include:

  • High fevers without improvement after initial antibiotic therapy
  • Relapsing symptoms following initial recovery
  • Symptoms such as hemolytic anemia, confusion, or persistent night sweats
  • Poor response to doxycycline, which does not treat certain co-infections like Babesia

Further diagnostic testing and consultation with an infectious disease specialist may be required when co-infection is suspected. Identifying and managing these overlapping infections can significantly improve outcomes and reduce long-term complications.

Limitations and Future Directions

Current tests have limitations—especially in the early stages. No single test can definitively confirm early Lyme disease in all patients.

Researchers are exploring newer tests, including:

Frequently Asked Questions (FAQs)

Q: Can someone have Lyme disease even if the test is negative?
Yes. In early infection, the immune system may not have produced detectable antibodies yet, which can lead to a false-negative result.

Q: What is the most reliable test for diagnosing Lyme disease?
The CDC-recommended two-tiered testing approach—an initial ELISA test followed by a confirmatory Western Blot or second EIA—is considered the standard for laboratory diagnosis.

Q: How soon after a tick bite should testing be done?
Testing is most accurate at least 2–4 weeks after exposure. If a characteristic rash (erythema migrans) develops, a clinical diagnosis may be made without testing.

Q: Do positive Lyme antibodies mean the infection is still active?
Not always. Antibodies can remain in the bloodstream long after the infection has resolved and do not necessarily indicate ongoing disease.

Q: Are at-home Lyme disease tests reliable?
Some at-home tests are FDA-cleared, but others are not. Results should always be reviewed and confirmed with a licensed healthcare provider.

[signup]

Key Takeaways

  • Lyme disease is caused by Borrelia burgdorferi and is primarily diagnosed through antibody testing.
  • The two-tiered testing approach (ELISA followed by Western Blot or a second EIA) remains the gold standard the CDC and FDA recommended.
  • Test timing is critical. Testing too early can lead to false negatives, and antibodies may take several weeks to become detectable.
  • A positive test does not always mean active infection, as antibodies can persist long after treatment.
  • Ticks may carry multiple pathogens, such as Anaplasma or Babesia, which can complicate symptoms and diagnosis.
  • While at-home Lyme tests may offer convenience, their accuracy varies. A healthcare provider should always confirm results.
  • Current testing has limitations in early disease, and research is ongoing to develop more accurate direct detection methods.
The information in this article is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose or treat any health problems or illnesses without consulting a doctor. Consult with a health care practitioner before relying on any information in this article or on this website.

Learn more

No items found.

Lab Tests in This Article

No lab tests!

Aziz, A., Christina Injan Mawang, & Ahamad, M. (2023). Direct Detection of Lyme Borrelia: Recent Advancement and Use of Aptamer Technology. Biomedicines, 11(10), 2818–2818. https://doi.org/10.3390/biomedicines11102818

Bryant, A. (2024, September 23). Autoimmune Disorders and Rheumatoid Arthritis: The Connection. Rupa Health. https://www.rupahealth.com/post/autoimmune-disorders-and-rheumatoid-arthritis-the-connection

CDC. (2024a, May 20). Clinical Testing and Diagnosis for Lyme Disease. Lyme Disease. https://www.cdc.gov/lyme/hcp/diagnosis-testing/index.html

CDC. (2024b, May 20). Lyme Disease Rashes. Lyme Disease. https://www.cdc.gov/lyme/signs-symptoms/lyme-disease-rashes.html

Cloyd, J. (2023, July 21). A Functional Medicine Fibromyalgia Protocol: Lab Testing, Therapeutic Diet, and Supplements. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-fibromyalgia-protocol-lab-testing-therapeutic-diet-and-supplements

Dattwyler, R. J., Volkman, D. J., Luft, B. J., Halperin, J. J., Thomas, J., & Golightly, M. G. (1988). Seronegative Lyme Disease. New England Journal of Medicine, 319(22), 1441–1446. https://doi.org/10.1056/nejm198812013192203

Ghosh, R., Joung, H.-A., Goncharov, A., Barath Palanisamy, Ngo, K., Katarina Pejcinovic, Krockenberger, N., Horn, E. J., Garner, O. B., Ghazal, E., O’Kula, A., Arnaboldi, P. M., Dattwyler, R. J., Ozcan, A., & Dino Di Carlo. (2024). Rapid single-tier serodiagnosis of Lyme disease. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-51067-5

Khakham, C. (2023a, April 10). The Best Diet for Chronic Epstein-Barr Virus. Rupa Health. https://www.rupahealth.com/post/the-best-diet-for-chronic-epstein-barr-virus

Khakham, C. (2023b, June 30). Integrative approaches to the treatment of lupus: A comprehensive review. Rupa Health. https://www.rupahealth.com/post/integrative-approaches-to-the-treatment-of-lupus-a-comprehensive-review

Pavletic, A. J., & Marques, A. R. (2017). Early Disseminated Lyme Disease Causing False-Positive Serology for Primary Epstein-Barr Virus Infection: Report of 2 Cases. Clinical Infectious Diseases, 65(2), 336–337. https://doi.org/10.1093/cid/cix298

Rupa Health. (n.d.). Lyme & Tickborne Disease Testing. Rupa Health. https://www.rupahealth.com/health-categories/lyme-tickborne-disease

Skar, G. L., & Simonsen, K. A. (2018, October 27). Lyme Disease. National Library of Medicine; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK431066/

Tudor, M. E., Al, A. M., & Gossman, W. G. (2024, August 17). Syphilis. Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK534780/

Order from 30+ labs in 20 seconds (DUTCH, Mosaic, Genova & More!)
We make ordering quick and painless — and best of all, it's free for practitioners.

Latest Articles

View more on Infections
Subscribe to the magazine for expert-written articles straight to your inbox
Join the thousands of savvy readers who get root cause medicine articles written by doctors in their inbox every week!
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Subscribe to the Magazine for free to keep reading!
Subscribe for free to keep reading, If you are already subscribed, enter your email address to log back in.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Are you a healthcare practitioner?
Thanks for subscribing!
Oops! Something went wrong while submitting the form.

Hey practitioners! 👋 Join Dr. Chris Magryta and Dr. Erik Lundquist for a comprehensive 6-week course on evaluating functional medicine labs from two perspectives: adult and pediatric. In this course, you’ll explore the convergence of lab results across different diseases and age groups, understanding how human lab values vary on a continuum influenced by age, genetics, and time. Register Here! Register Here.

Hey practitioners! :wave: Join Dr. Cheryl Burdette, ND for a free webinar, "Understanding Immune Balance in Autoimmunity," on Thursday, May 7th, at 09:00AM PT / 12:00PM EST.

In this class, you'll gain insight into how gut health and immune balance may be connected, the role of key markers like Zonulin and oxidative stress indicators, and strategies to help support gut barrier integrity and immune resilience.

Register now to secure your spot!