This is a unique instance of fatal fat embolism secondary to bone marrow necrosis in a patient with sickle cell-hemoglobin C disease, systemic lupus erythematosus, and Sjögren's syndrome. An elevated level of IgG and treatment with corticosteroids appeared to be major factors in the death of this patient. This complication occurs most often in patients with sickle cell-hemoglobin C disease, especially in pregnant women near term. It should be suspected in any patient with sickle cell disease in whom unexplained fever, respiratory, and neurologic symptoms typical of fat emboli develop following the onset of bone pain. Exchange blood transfusion may be lifesaving.