Infectious mononucleosis is typically a self-limited viral infection of adolescence and early adulthood that resolves in a period of weeks, causing no major sequelae. We describe a case of a healthy 18-year-old female diagnosed with infectious mononucleosis who also presented with right upper quadrant abdominal pain, moderate transaminitis, and cholestatic biochemistry. An ultrasound revealed acute acalculous cholecystitis, generally a condition seen in the context of critical illness. Further investigating emergency department patients with infectious mononucleosis is often not indicated, but may be important for those who present atypically.