The objective of the present study was to examine the effects of pre-exercise NaHCO₃ administration to induce metabolic alkalosis, on the arterial oxygenation in racehorses performing maximal exercise. Two sets of experiments, IV physiological saline and NaHCO₃ (250mg/kg, IV), were carried out on 13 healthy, sound Thoroughbred horses in random order, 7 days apart. Blood-gas variables were examined at rest and during incremental exercise leading to 120 s of galloping at 14 m/s on a 3.5% uphill grade, which elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. NaHCO₃ administration caused alkalosis and hemodilution in standing horses, but arterial O₂ tension and hemoglobin-O₂ saturation were unaffected. Thus, NaHCO₃ administration caused a reduction in arterial O₂ content at rest, although the arterial to mixed-venous blood O₂ content gradient was unaffected. During maximal exercise in both treatments, arterial hypoxemia, desaturation, hypercapnia, acidosis, hyperthermia and hemoconcentration developed. Although the extent of exercise-induced arterial hypoxemia was similar, there was an attenuation of the desaturation of arterial hemoglobin in the NaHCO₃ treated horses, which had higher arterial pH. Despite these observations, the arterial blood O₂ content of exercising horses was less in the NaHCO₃ experiments because of the hemodilution, and an attenuation of the exercise-induced expansion of the arterial to mixed-venous blood O₂ content gradient was observed. It was concluded that pre-exercise NaHCO₃ administration does not affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise.