We investigated the effects of two carbohydrate-based sports drinks on fluid intake and immunoendocrine responses to cycling. Six well-trained male cyclists completed trials on three separate days that involved cycling at 60% VO_2peak for 90 min in hot conditions (28.1±1.5ºC and 52.6±3.1% relative humidity). During each trial, the subjects consumed ad libitum (1) an isotonic sports drink (osmolality 317 mOsm/kg), (2) a hypotonic sports drink (osmolality 193 mOsm/kg) or (3) plain water. The cyclists consumed significantly (p<0.05) more of the isotonic drink (1.23±0.35 L) and hypotonic drink (1.44±0.55 L) compared with water (0.73±0.26 L). Compared with water (−0.96±0.26 kg), body mass decreased significantly less after consuming the hypotonic drink (−0.50±0.38 kg) but not the isotonic drink (−0.51±0.41 kg). Blood glucose concentration was significantly higher at the end of the isotonic and hypotonic drink trials compared with the water trial. Neutrophil count and the plasma concentrations of catecholamines, interleukin 6 (IL-6), myeloperoxidase, calprotectin and myoglobin increased significantly during all three trials. IL-6 and calprotectin were significantly lower following the hypotonic drink trial compared with the water trial. In conclusion, hypotonic sports drinks are appealing for athletes to drink during exercise, and may help to offset fluid losses and attenuate some inflammatory responses to exercise.