Mono or Lyme Disease? Why Symptoms Can Be Confused
Quick Answer: Mono (Epstein-Barr virus) and Lyme disease can cause similar symptoms—and in some cases, patients may have both at the same time.
Clinical Insight: A positive mono test does not rule out Lyme disease. Overlapping symptoms and cross-reactivity can delay diagnosis.
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, they may occur together.
Why Mono and Lyme Disease Are Confused
Both mono and Lyme disease can cause:
- Fatigue
- Fever
- Sore throat
- Joint pain
- Swollen lymph nodes
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.
Studies have documented patients with laboratory evidence of both Lyme disease and Epstein-Barr virus (EBV) infection within a short time frame.
This means clinicians should not assume a single diagnosis when symptoms overlap.
Why Testing Can Be Misleading
Testing for mono and Lyme disease can be confusing:
- EBV (mono) tests may be positive during or after infection
- Lyme serology may be dismissed as cross-reactivity
A positive mono test does not exclude Lyme disease.
This can contribute to delayed Lyme disease diagnosis.
Case Examples: When Diagnosis Is Missed
Case reports illustrate how confusion can occur:
- A child diagnosed with mono later developed erythema migrans consistent with Lyme disease
- Another patient initially treated for Lyme disease was later found to have mono as well
Both patients recovered after appropriate diagnosis and treatment.
When to Suspect Lyme Disease Instead of Mono
Consider Lyme disease when:
- Symptoms persist longer than expected for mono
- A rash develops (especially erythema migrans)
- Joint symptoms are prominent
- There is a history of tick exposure
Symptoms that evolve or don’t follow a typical mono pattern should raise concern.
Why Early Recognition Matters
Missing Lyme disease can lead to complications such as:
- Neurologic involvement
- Lyme carditis
- Persistent symptoms
Early diagnosis allows for appropriate treatment and improved outcomes.
Clinical Takeaway
Mono and Lyme disease can look similar—and may occur together.
When symptoms overlap or do not follow a typical course, clinicians should consider both conditions.
Recognizing this pattern can prevent delayed diagnosis and improve care.
See also Lyme disease overview.
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.