Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE) very rarely present simultaneously and pose a diagnostic and therapeutic dilemma to the critical care team. Prompt diagnosis and management with plasma exchange and immunosuppression is life-saving. A patient critically ill with TTP and SLE, successfully managed in the acute period of illness with plasma exchange, steroids and mycophenolate mofetil is described