A 62-year-old woman with an unremarkable medical history was admitted to our hospital with severe diarrhea and frequent vomiting. She was diagnosed with infectious colitis and dehydration, and was subsequently treated with adequate fluid management; however, her clinical condition did not improve. Laboratory findings indicated the presence of thrombocytopenia, renal insufficiency, and rhabdomyolysis. Her serum ferritin level was extremely high, and bone marrow aspiration showed evidence of phagocytic histiocytes. Based on these findings, the patient was diagnosed with hemophagocytic syndrome (HPS) and treated by intravenous administration of prednisolone, following which her condition improved drastically the next day. HPS is a rare condition characterized by high fever, hepatosplenomegaly, multiple organ dysfunction, coagulopathy, and pancytopenia. It is caused by cytokine overproduction, resulting in uncontrolled hemophagocytosis, and can be classified as primary or secondary depending on various clinical conditions. HPS with viral infections or malignant lymphoma is well documented. This report describes a rare case of secondary HPS associated with bacterial colitis and demonstrates that unexplained fever, thrombocytopenia, and multiple organ dysfunction should be investigated to eliminate the possibility of HPS in critical care settings.