Perisplenitis is a rare condition that refers to inflammation of the peritoneal covering of the spleen that causes an acute, pleuritic-type left upper quadrant abdominal pain. Perisplenitis occurs in the setting of splenomegaly. Splenomegaly most typically develops from infections, such as peritonitis, pelvic inflammatory disease, endocarditis, sepsis, malaria with resultant splenomegaly, or viral infections that can cause splenomegaly (eg, Epstein-Barr virus). Perisplenitis has also been described in sickle cell disease, thalassemia (alpha and beta), and lymphoma, all of which can cause splenomegaly.