Hyperthermal stress and resulting free radical generation is known to impair endurance capacity and immune cell redistribution during prolonged exercise. Caffeic acid phenethyl ester (CAPE), a phenolic compound purified from propolis, has many biological and pharmacological activities including antioxidation. To examine whether CAPE has protective effect against hyperthermal stress in athletes, we isolated peripheral blood mononuclear cells (MNC) from competitive cyclists and assessed their response to hyperthermia with or without CAPE pretreatment. We found that pretreatment of cyclists' MNC with CAPE (0, 1, 2, 4 microg/mL) reversed or reduced hyperthermia-induced survival inhibition, necrosis, superoxide production, glutathione depletion, and intracellular superoxide burst in a dose-dependent manner. These results suggest that CAPE may enhance the hyperthermal tolerance in immune mononuclear cells of competitive cyclists.