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Described herein is the case of a previously healthy 7-year-old girl who had splenic infarction. This lesion was identified 1 day after the first presentation of peri-umbilical and right upper quadrant pain. She had abnormal hepatic function and mild splenomegaly, and was diagnosed as having primary Epstein–Barr virus (EBV) infection. Coagulation profiles indicated low plasma activity of protein C (49%) and protein S (47%), which normalized 3 weeks later. Hypercoagulability in transient protein C and protein S deficiency might contribute to the development of splenic infarction in infectious mononucleosis.