Splenic infarction is a rare and likely underdiagnosed complication of Epstein-Barr virus (EBV) associated infectious mononucleosis (IM). Here we describe an 18-year-old male with persistent severe left-sided abdominal pain found to be EBV positive and have a large splenic infarct, along with a transient decrease in protein C, protein S, and antithrombin III activity levels. He was treated with supportive care, and anticoagulated with heparin and apixaban. We review prior reports and perspectives on underlying pathophysiology, diagnosis, and the management of these cases which likely does not require anticoagulation although may be considered on a per case basis.