Sickle cell trait is a relatively common condition in the African-American population. Individuals with this condition may have any of several complications under rare circumstances. We report a patient who presented with extensive compartment syndrome leading to death. A 31-year-old African-American male with known history of sickle cell trait developed extensive compartment syndrome followed by rhabdomyolysis, severe acidosis, acute renal failure, and coagulopathy. Although the patient underwent multiple fasciotomies for extensive compartment syndrome and received aggressive resuscitation with massive transfusions of blood, blood products and intravenous fluids, he died. Multiple compartment syndromes in patients with sickle cell trait represent a very unusual complication and can cause significant morbidity and mortality. Avoidance of strenuous exercise, especially in hot climates, early diagnosis, and aggressive therapy are very important to prevent this catastrophic complication.