Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors. Others have hypothesized some of the aforementioned factors combining in a "perfect storm" to trigger ECAST with a resultant potentially fatal "metabolic crisis." This case report provides a brief review of SCT as it pertains to exercise in warfighters and athletes, identifies known and postulated risk factors associated with ECAST, and introduces the potential mechanistic role of the "double hit" as a contributor to ECAST.
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