Near infrared spectroscopy (NIRS) may provide valuable insight into the determinants of exercise performance. We examined the effects of severe hypoxia on cerebral (prefrontal lobe) and muscle (gastrocnemius) oxygenation at rest and during a fatiguing task. After a 15-min rest, 15 healthy subjects (age 25.3 +/- 0.9 yr) performed a sustained contraction of the ankle extensors at 40% of maximal voluntary force until exhaustion. The contraction was performed at two different fractions of inspired O2 fraction (F(IO2) = 0.21/0.11) in randomized and single-blind fashion. Cerebral and muscle oxy-(HbO2) deoxy-(HHb) total-hemoglobin (HbTot) and tissue oxygenation index (TOI) were monitored continuously by NIRS. Arterial O2 saturation (SpO2) was estimated by pulse oximetry throughout the protocol. Muscle TOI did not differ between normoxia and hypoxia after the 15-min rest, whereas SpO2 and cerebral TOI significantly dropped (-6.5 +/- 0.9% and -3.9 +/- 1.0%, respectively, P<0.05) in hypoxia. The muscle NIRS changes during exercise were similar in normoxia and hypoxia, whereas the increased cerebral HbTot and HbO2 near exhaustion were markedly reduced in hypoxia. In conclusion, although F(IO2) had no significant effect on endurance time, NIRS patterns near exhaustion in hypoxia differed from normoxia.