Staphylococcal toxic shock syndrome (STSS) is an acute, toxin-mediated febrile illness that rapidly leads to multiple organ dysfunction syndromes, and systemic lupus erythematosus (SLE) is a multisystem autoimmune and inflammatory disease. Differential diagnosis in STSS involved a number of common diseases associated with a wide range of nonmenstrual-related conditions, including SLE. Therefore, it is difficult to distinguish from each other initially. We report a case of concurrent fatal STSS and SLE who was treated as sepsis initially, which leads to grave prognosis.