Mono or Lyme Disease? Why Symptoms Can Be Confused
Mono and Lyme disease can cause similar symptoms, including fatigue, fever, sore throat, swollen glands, and joint pain.
A positive test for mono does not always rule out Lyme disease.
Fatigue. Fever. Sore throat. Joint pain.
Is it mono—or could it be Lyme disease?
These two conditions can look very similar, and in some cases, patients may have both infections at the same time.
Why Mono and Lyme Disease Are Confused
Mono, most often caused by Epstein-Barr virus (EBV), and Lyme disease can present with remarkably similar symptoms.
Both may cause:
- Fatigue
- Fever
- Sore throat
- Joint pain
- Swollen lymph nodes
- Body aches
This overlap can make diagnosis difficult, especially early in illness.
See the broader Lyme disease symptoms guide.
Can You Have Both Mono and Lyme Disease?
Yes. Published case reports have described patients with laboratory evidence of both Lyme disease and EBV infection within a short time frame.
Koester and colleagues described two children with confirmed early Lyme disease and clinical features suggestive of infectious mononucleosis.
These cases highlight an important point: clinicians should not assume a single diagnosis when symptoms overlap.
Case 1: Mono Diagnosis Delayed Lyme Recognition
A 5-year-old boy living in a Lyme-endemic region developed abdominal pain, intermittent fevers, neck pain, fatigue, and sore throat.
He had no known tick bite or rash.
Testing suggested mononucleosis, and his Lyme test was initially dismissed as possible cross-reactivity.
Two days later, he returned with multiple erythema migrans rashes consistent with early disseminated Lyme disease.
He was treated with amoxicillin and improved rapidly.
Case 2: Lyme Disease and Mono Occurred Together
An 8-year-old boy developed fevers, headache, sore throat, abdominal pain, fatigue, muscle aches, and joint pain.
He had no known rash or tick bite.
He was diagnosed and treated for Lyme disease, but one week later continued to have fevers and worsening abdominal and joint pain.
Further evaluation suggested active EBV infection, and repeat Lyme testing showed seroconversion.
After treatment, the child made a complete recovery.
Why Testing Can Be Misleading
Testing for mono and Lyme disease can be confusing because serologic cross-reactivity may occur.
Some EBV infections may produce false-positive Lyme IgM results.
However, dismissing Lyme test results solely because mono is suspected can delay diagnosis and treatment.
Heterophile antibody and EBV testing should not be used by themselves to exclude Lyme disease.
This diagnostic confusion can contribute to delayed Lyme disease diagnosis.
When to Suspect Lyme Disease Instead of Mono
Consider Lyme disease when symptoms do not follow the expected course of mono.
Clinical clues may include:
- Erythema migrans rash
- Known or possible tick exposure
- Prominent joint pain
- Neurologic symptoms
- Symptoms that persist longer than expected
- Failure to improve with supportive care alone
Learn more about Lyme disease misdiagnosis.
Why Early Recognition Matters
Missing Lyme disease can lead to complications, especially when treatment is delayed.
Potential complications may include neurologic involvement, Lyme carditis, arthritis, and persistent symptoms.
See also neurologic Lyme disease.
Early recognition allows for more appropriate treatment and follow-up.
Frequently Asked Questions
Can mono and Lyme disease cause the same symptoms?
Yes. Both can cause fatigue, fever, sore throat, swollen lymph nodes, body aches, and joint pain.
Can someone have mono and Lyme disease at the same time?
Yes. Published case reports have described patients with evidence of both EBV infection and Lyme disease.
Does a positive mono test rule out Lyme disease?
No. A positive mono test does not automatically rule out Lyme disease, especially when symptoms, rash, tick exposure, or Lyme testing suggest otherwise.
Can EBV cause a false-positive Lyme test?
Yes. EBV infection can sometimes contribute to false-positive Lyme IgM results, which is why clinical context is important.
When should Lyme disease be considered after a mono diagnosis?
Lyme disease should be considered when symptoms persist, evolve, include joint or neurologic findings, or occur after possible tick exposure.
Clinical Takeaway
Mono and Lyme disease can look similar, and in some cases, patients may have both infections at the same time.
When symptoms overlap or do not follow a typical course, clinicians should avoid diagnostic closure and consider both conditions.
A positive mono test should not automatically exclude Lyme disease when the clinical picture suggests tick-borne illness.
Related Articles
When Lyme Disease Causes a Positive Test for Mononucleosis
Pediatric Lyme Disease
Post-Treatment Lyme Disease Syndrome
Autonomic Dysfunction and Lyme Disease
Lyme Coinfections
References
- Koester TM, Meece JK, Fritsche TR, Frost HM. Infectious Mononucleosis and Lyme Disease as Confounding Diagnoses: A Report of 2 Cases. Clin Med Res. 2018.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
Bonnie Bennett had some interesting historical remarks about borreliae /ebv testing in her book “Tick Bites & MS…”
also referenced, although regarding viruses more generally in her correspondence with Burgdorfer,
https://contentdm.uvu.edu/cdm/singleitem/collection/Burgdorfer/id/47/rec/51
I’ve had EBV twice, the first time resulted in insomnia of the worst kind, the 2nd time it resulted in the worst CFS like I was in a coma. I’ve never had any Dr even offer help. I struggle through treating myself with illegal stimulants which is far from ideal but without it I would be bedbound once again. I wish someone cared and offered help.
Some patients in my practice thought to have EBV were diagnosed with Lyme disease.
I think this might be my issue. My son was diagnosed with mono about 1 month agobut has since moved out. I started feeling flu like symptoms, vision changes as well as neck pain and then found a tick on the back of my head about 3 weeks ago. Had test results reactive to 4 bands that made lyme dusease equivocal. I am being treated with antibiotics but was not tested for mono. No soar throat but swollen glands and lymphnodes. Mental fog as well and achy all over. Feel horrible.
Hi Dr.Cameron,
I had Lymes disease and mono at the same time as a freshman college. About a year later I had mono again, followed by chronic tonsilitis. I ended up having a tonsillectomy and my health seemed to improve dramatically. However, I recently went to the doctor (less than a year since my tonsillectomy) and they say I have mono again. I’m wondering if the Lymes disease & mono combo just wrecked my immune system. Do you have any medical centers or doctors you recommend that I see? Since I’ve been in college I haven’t been consistently seeing the same doctor, which hasn’t helped.
I find Mono and Lyme disease look alike in my patients. I look a second time at Lyme disease. I also look for other illnesses. I would check with services like Global Lyme Alliance, Lyme disease association and ILADS.
Hi Dr. Cameron,
I had EBV 3 times since 2014. Last April of 2019, I had EBV and Lyme disease concurrently. Treated for Lyme disease for the first time. I got better after 2 months. Yet, in November 2019, my symptoms came back again. Never thought I had both diseases again! Yet, I am just diagnosed with EBV and Lyme disease concurrently again! Extreme fatigue with cardiac symptoms (palpation upon any physical activity). I am just hoping there is some doctor nearby who can truly listen and treat accordingly. Dr. Cameron, do you have any doctor to recommend? I live in Maryland. Is there any support group for people suffering like me? I’d appreciate your help.
You could contact a support group or request assistance from the Global Lyme Alliance, ILADS, or Lyme Disease Association. You can also call my office in New York.