Liver injury is a well-known complication of exertional heat stroke. However severe acute irreversible liver dysfunction is rarely associated. Persistent centrolobular hepatocellular necrosis without any regeneration remains very uncommon. We report a case of fatal acute liver failure occurring after exertional heat stroke. Despite the conventional symptomatic treatment, especially active cooling, the patient experienced multiple organ failure with brain death 6 days after his admission. In this case, a chronic treatment with neuroleptic and anticholinergic agents may be considered as a predisposing factor.