The study examined the progression of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after infectious mononucleosis (IM) in college students from a diverse socioeconomic and ethnic population over 7 years. Participants were assessed at four time points: pre-MI (baseline), within 6 weeks of MI diagnosis, 6 months post-MI, and 7 years later, measuring health status, psychological functioning, and blood biomarkers. About 30% of ME/CFS cases are associated with Epstein-Barr virus infection, which causes MI. At 7-year follow-up, 81% of participants with initially severe ME/CFS continued to meet diagnostic criteria. Conversely, only about one-third of those with moderate or persistent symptoms at 6 months still had ME/CFS at 7 years. Findings show that ME/CFS after MI persists for a long time especially in patients with a severe course at the beginning.