This study presents a series of 16 carriers of hemoglobin S (HbS) who died during various circumstances. Many of the cases were associated with mild to moderate exertion. The onset and/or duration of symptoms varied from a few minutes to several hours with many displaying a prolonged lucid interval with stable vital signs. Despite seeking medical treatment, sickle cell trait-related micro-occlusive crisis was never considered in the differential diagnosis. Several cases were associated with sudden death. In those deaths which were delayed, high anion gap and uncompensated metabolic acidosis were typical and were not heat related. Also characteristic were large increases in creatine kinase, alanine aminotransferase, and aspartate aminotransferase along with myoglobinemia. Although the antemortem diagnosis of rhabdomyolysis was made, the underlying cause was never deduced by the clinicians. The sickling found at autopsy is not always a postmortem artifact, and in the right circumstances can be diagnostic.