Complications of Mononucleosis
Infectious DiseasesMononucleosis

What Are the Long-Term Complications of Mononucleosis?

What Are the Long-Term Complications of Mononucleosis?
Everyday Health
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Updated on December 1, 2025
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Mononucleosis (mono) usually results from an infection with the Epstein-Barr virus (EBV). Symptoms of mono include exhaustion, fever, muscle aches, and a sore throat. These usually subside after around two weeks. But some people have longer-term effects.

After the main symptoms disappear, fatigue, swollen lymph nodes, and a swollen spleen may continue for several more weeks or months. After that, most people recover fully.

But the EBV virus remains in your body after mono clears up and can sometimes reactivate, causing new health problems later in life.

In rare cases, high levels of the virus can stay in your blood after mono, resulting in long-term effects of mono and varied health problems, some of which can be severe.

Here, we look at some of the complications of mono and EBV that can develop if the virus stays at high levels or reactivates.

Mono Can Cause a Number of Complications

Mono symptoms usually clear up within two to four weeks, but some may linger or become severe.

Enlarged Spleen

The most common serious complication of mono is an enlarged spleen (splenomegaly). The spleen is an organ in your upper left abdomen that plays a crucial role in your immune system and also filters your blood.

If the spleen becomes too swollen, it can rupture if you fall or someone bumps into you. In rare cases, it can rupture spontaneously in a person with mono.

A ruptured spleen can lead to life-threatening internal bleeding. Seek immediate medical attention if you have mono and feel a sudden, sharp pain on the left side of your upper abdomen, especially if it worsens when you take a deep breath, or if you develop signs of anemia like lightheadedness, fainting, fast heart rate, pale skin, or difficulty breathing, especially with activity.

To protect your spleen during mono, you’ll need to avoid strenuous activity and contact sports until your doctor says it’s safe to return to them, which may be up to one to two months after onset of infection.

Other Complications

Other complications of mono include:

  • Mild liver inflammation, known as hepatitis
  • Jaundice, a yellowing of the whites of your eyes or your skin due to liver problems
  • Swollen lymph nodes
  • Swollen tonsils, which may make it hard to breathe

Less-Common Complications

Less-common complications include:

  • Thrombocytopenia: A low level of platelets, the blood cells needed for clotting
  • Anemia: Low levels of red blood cells and hemoglobin, leading to fatigue and breathlessness
  • Myocarditis: an inflammation of the heart muscle
  • Nervous system complications, such as meningitis

Rare Complications From Chronic Mono

EBV is one of the most common viruses in the world.

EBV usually enters a person’s body through saliva. When you first have the virus, you might either have no symptoms or develop the symptoms of mono.

As we have seen, the symptoms and even complications of mono usually clear up after a few weeks or months.

But, like other herpes viruses, EBV stays in your body once it’s there. Mostly, it’s inactive and doesn’t cause any further symptoms. In fact, you might not know you have it unless you have a blood test.

In some people, however, it can reactivate and cause ongoing complications, some of which can be severe.

Increased Risk of Cancer

EBV is one of a group of viruses known as oncoviruses. These are viruses that appear to increase the risk of cancer.

EBV may increase your risk of:

  • Cancer in your nose and upper throat (nasopharyngeal cancer)
  • Certain types of lymphoma, including Hodgkin and non-Hodgkin

  • Stomach cancer

  • Soft-tissue cancers

People who have had an organ transplant are more likely to experience EBV complications because they need drugs to stop their body from rejecting the new organ.

 The drugs do this by suppressing the immune system. A transplant can also cause your body to produce too many white blood cells, which can lead to a type of cancer known as lymphoproliferative disorder.

Link to Autoimmune Diseases

Some research suggests there may also be links between EBV and certain autoimmune diseases, such as multiple sclerosis (MS) and myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).

Research suggests MS is more likely to occur in people with EBV and unlikely in those who don’t have it.

Most people with MS carry EBV, according to Henry Balfour Jr., MD, a professor emeritus in the department of laboratory medicine and pathology in the department of pediatrics at the University of Minnesota Medical School in Minneapolis.

Experts have also linked mono caused by EBV with the development of ME/CFS in children, teens, and young adults. Symptoms of ME/CFS include persistent, severe fatigue, difficulty thinking, and ongoing pain.

Precisely why or how ME/CFS happens remains unclear, but it often occurs after a viral infection, such as mono.

Chronic Active Epstein-Barr Virus (CAEBV): When Mono Doesn’t Go Away

Chronic active Epstein-Barr virus (CAEBV) is a rare disorder. It’s when you continue to have high levels of the EBV virus in your blood because your immune system can’t suppress it.

You may have ongoing symptoms of mono and inflammation throughout your body that can affect your eyes, liver, vascular system, and more.

For some people, symptoms remain stable and they don’t need treatment. For others, symptoms can develop and worsen quickly and may become life-threatening.

Treatment with antiviral agents may help, but stem cell transplants may be more successful as a treatment.

Who’s at Risk for Post-Mono Complications?

You’re most likely to have severe symptoms or complications if you have a weakened immune system, according to Eric Johannsen, MD, an associate professor of infectious diseases and an EBV expert at the University of Wisconsin School of Medicine and Public Health in Madison.

This could be due to:

  • HIV and other diseases that affect your immune system
  • Certain drugs that suppress your immune system after an organ transplant, or drugs to treat an autoimmune disease
  • Some cancers and cancer treatments
EBV is the most common cause of mono but not the only one. Mono due to EBV doesn’t usually come back, although some studies suggest this could happen. If you have mono symptoms a second time, it could be due to another cause, such as:

  • Toxoplasmosis
  • Cytomegalovirus infections
  • Rubella
  • Hepatitis A, B, or C
  • HIV

When to Call Your Doctor or Seek Medical Attention

If you have any of the following symptoms, seek medical care right away. They could be a sign of a complication that needs attention, Dr. Balfour says.

  • Difficulty breathing
  • Sudden and sharp pain on the upper left side of your abdomen, a sign of a rupture in your spleen
  • Fainting or severe dizziness
  • Fast heart rate (>110) that doesn’t improve when fever is low
  • High fever (101.5 degrees F or higher) that won’t go away
  • Problems swallowing
  • Severe headache
  • Noticeable yellow color in eyes and skin (a sign of jaundice)
  • Weakness in the arms and legs
You should also seek medical advice if you have manageable symptoms but they don’t go away after two weeks.

The Takeaway

  • Mononucleosis is a contagious viral infection, most commonly caused by the Epstein-Barr virus (EBV).
  • Symptoms of mono usually improve after two to four weeks but can last longer.
  • Severe symptoms can also occur, such as a swollen or ruptured spleen, meningitis, or an inflamed heart muscle.
  • There can also be long-term complications of mono and EBV.
  • In people with a weakened immune system, EBV can reactivate later and cause further complications, such as certain types of cancer.
  • It’s best to see a doctor if you have mono or are concerned about long-term symptoms or complications.

Resources We Trust

EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
  1. Mayo Clinic Staff. Mononucleosis: Overview. Mayo Clinic. November 30, 2022.
  2. About Epstein-Barr Virus. Centers for Disease Control and Prevention. May 9, 2024.
  3. Hoover K et al. Epstein-Barr Virus. StatPearls. August 8, 2023.
  4. What Is Epstein-Barr Virus and How Can It Impact Cancer Risk? American Cancer Society. December 20, 2024.
  5. Kawada J et al. Updated Guidelines for Chronic Active Epstein-Barr Virus Disease. International Journal of Hematology. September 20, 2023.
  6. Mayo Clinic Staff. Enlarged Spleen (Splenomegaly): Overview. Mayo Clinic. August 25, 2023.
  7. Leung AKC et al. Infectious Mononucleosis: An Updated Review. Current Pediatric Reviews. August 7, 2023.
  8. Clinical Overview of Epstein-Barr Virus (EBV). Centers for Disease Control and Prevention. April 10, 2024.
  9. Bjornevik K et al. Epstein-Barr Virus as a Leading Cause of Multiple Sclerosis: Mechanisms and Implications. Nature Reviews Neurology. February 9, 2023.
  10. Pricoco R et al. One-Year Follow-Up of Young People With ME/CFS Following Infectious Mononucleosis by Epstein Barr Virus. Frontiers in Pediatrics. January 18, 2024.
  11. Immunocompromised (Immunosuppressed). Cleveland Clinic. December 17, 2024.
  12. Mayo Clinic Staff. Mononucleosis: Can it recur? Mayo Clinic. February 11, 2023.
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Amy Walsh, MD, MDP, is a board-certified emergency physician at HealthPartners. She has 15 years of experience, fellowship training in global emergency medicine, and extensive experience in rural emergency medicine.

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