What is the recommended treatment for infectious mononucleosis (mono)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: December 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Treatment of Infectious Mononucleosis

Treatment for infectious mononucleosis is entirely supportive, as antiviral medications like aciclovir do not improve outcomes in otherwise healthy individuals. 1

Supportive Care Measures

The cornerstone of management involves symptom relief and activity modification:

  • Adequate hydration, analgesics, and antipyretics are the primary interventions for symptom control 2
  • Rest should be guided by the patient's energy level rather than enforced bed rest 2
  • Fatigue may persist for several months after acute infection resolves, which is normal and expected 2, 3

Activity Restrictions

Patients must avoid contact sports and strenuous exercise for 8 weeks from symptom onset or while splenomegaly persists, whichever is longer 4, 2. This is critical because splenic rupture, though rare (0.1-0.5% of cases), is the most feared and potentially fatal complication 4, 3.

Role of Corticosteroids

Corticosteroids should be reserved exclusively for airway obstruction or severe pharyngeal edema causing respiratory compromise 1. Despite their common use in practice, the evidence does not support routine steroid use:

  • A Cochrane systematic review of seven trials (362 participants) found no sustained benefit for symptom control with steroids 5
  • While two trials showed transient improvement in sore throat at 12 hours, this benefit was not maintained 5
  • Serious complications have been documented with prolonged steroid use, including septic shock, polymicrobial bacteremia, and septic emboli 6
  • The risk-benefit ratio does not favor routine steroid use in uncomplicated cases 5

What Does NOT Work

Aciclovir and other antiviral agents are ineffective and should not be prescribed for infectious mononucleosis in immunocompetent patients 1. Similarly, antihistamines have no role in routine treatment 2.

Special Populations

For immunocompromised patients with suspected primary EBV infection:

  • Reduce or discontinue immunomodulator therapy if clinically feasible 1
  • Obtain complete blood count, blood film, and liver function tests 1
  • These patients require specialist consultation due to increased risk of EBV-associated lymphoproliferative disease 1

Common Pitfalls to Avoid

  • Do not prescribe antibiotics empirically for pharyngitis without confirming streptococcal infection, as the classic maculopapular rash occurs in 10-45% of mononucleosis patients and is dramatically worsened by ampicillin or amoxicillin 4, 2
  • Do not use steroids for routine symptom control despite patient or family pressure, as evidence shows no benefit and potential harm 5, 6
  • Do not clear patients for contact sports prematurely, even if they feel better, as splenic rupture can occur weeks after symptom onset 4, 2

References

Guideline

Diagnosis and Treatment of Infectious Mononucleosis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Epstein-Barr virus infectious mononucleosis.

American family physician, 2004

Research

Diagnosis and treatment of infectious mononucleosis.

American family physician, 1994

Research

Infectious Mononucleosis: An Updated Review.

Current pediatric reviews, 2024

Research

Steroids for symptom control in infectious mononucleosis.

The Cochrane database of systematic reviews, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.