Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is a representative community-associated MRSA (CA-MRSA) clone around the world. We herein report a patient of USA300 clone infection who could not be saved. A 25-year-old man who had sex with men presented with fever lasting one week and skin lesions on the buttocks. Computed tomography imaging showed the findings of multiple nodules and consolidations, especially in the peripheral lung fields, right iliac vein thrombosis, and pyogenic myositis of bilateral medial thighs. Blood cultures revealed MRSA bacteremia. The conditions of the patient deteriorated rapidly, complicated by acute respiratory distress syndrome and infective endocarditis, and was finally intubated on the 6th hospital day and died on the 9th day. Multilocus sequence typing of this patient’s MRSA strain was sequence type 8, had a staphylococcal cassette chromosome of mec type IVa, Panton-Valentine leukocidin gene, and the arginine catabolic mobile element, indicating it was USA300 clone. Past literatures suggest that CA-MRSA skin lesions presenting with furuncle or carbuncle on the lower body are at a high risk for severe disease. The patient’s background and appearance as well as the location of the skin lesions should be critical for the early diagnosis of severe CA-MRSA infection.