During prolonged exercise in the heat, the brain temperature may increase to well above 40°C as heat removal by the cerebral circulation becomes inadequate to match the cerebral metabolic heat production (Nybo et al., 2002). Heat is consequently stored in the brain and the mental effort associated with exercise increases in step with the rise in brain temperature (Nybo & Secher NH, 2004). Under such exercise conditions, intra nasal cooling, specific cooling of the neck or cooling of the face does not affect the average brain temperature (Nybo & Secher, 2011). Also, the cerebral metabolic rate for oxygen increases as consequence of the elevated temperature, but paradoxically the cerebral blood flow becomes reduces as hyperthermia-induced hyperventilation lowers the arterial carbon dioxide tension. Hence, the cerebral mitochondrial oxygen tension becomes reduced, but the reduction is modest and apparently not the main factor influencing the central fatigue that arises secondary to hyperthermia (Rasmussen et al., 2010). The present presentation provides an up-to-date overview of the cerebral changes occurring during prolonged exercise in the heat – with special reference to those of importance for fatigue and motor performance. References Nybo L & Secher NH (2004). Cerebral perturbations provoked by prolonged exercise. Prog Neurobiol 72, 223-261. Nybo L & Secher NH (2011). Last Word on Point:Counterpoint: Humans do/do not demonstrate selective brain cooling during hyperthermia. J Appl Physiol 110, 582. Nybo L, Secher NH, & Nielsen B (2002). Inadequate heat release from the human brain during prolonged exercise with hyperthermia. J Physiol 545, 697-704. Rasmussen P, Nybo L, Volianitis S, Moller K, Secher NH, & Gjedde A (2010). Cerebral oxygenation is reduced during hyperthermic exercise in humans. Acta Physiol (Oxf) 199, 63-70.