The pathophysiological process of exercise-induced death in subjects with sickle cell trait (SCT) remains unclear. Concerning the cause of death, authors have suggested stressful environmental conditions such as altitude, heat and humidity, or abnormal patient conditions such as deconditioning, fatigue, and disease. These conditions are thought to lead to hypoxemia, hyperlactatemia, acidosis, dehydration, hyperthermia, or exercise-induced rhabdomyolysis, all of which may initiate sickle cell crisis, disseminated intravascular coagulation, myoglobinuria, and renal failure. We report the case of a 41-yr-old, healthy, and apparently well-conditioned subject with SCT who died during a cross-country race under normal environmental conditions in good weather (in terms of temperature and humidity). The medical and athletic history of the subject were unremarkable. We refer to an epidemiological study that reported a relation between age and exercise-induced sudden death in subjects with SCT. We then review the pathophysiological effects of aging in association with deconditioning and high-level training reported in the literature, particularly the decrease in aerobic metabolism in deconditioned subjects, and the exercise-induced hypoxemia in highly trained subjects. We discuss the consequences of deconditioning and high-level training in subjects with SCT during exercise, and conclude that these factors may be involved in the age-dependent risk of exercise-related sudden death in subjects with SCT.