A 58-year-old female was admitted due to severe sepsis and multi-organ failure with a fulminant purpuric rash. Meropenem, vancomycin and levofloxacin were administered, although no focus of infection was detected. However, computed tomography revealed a profoundly hypoplastic spleen, and a blood smear detected Howell-Jolly bodies. Blood cultures grew Streptococcus pneumoniae (serotype 22F) three hours after admission. The patient was finally diagnosed as overwhelming pneumococcal sepsis with hyposplenism precipitated by splenic hypoplasia. Clinicians should pay attention to the splenic size and Howell-Jolly bodies in cases of sepsis of unknown origin.