Aim: To investigate the effect of carbon monoxide (CO) in the inspired air as anticipated during peak hours of traffic in polluted megalopolises on cerebral, respiratory and leg muscle oxygenation during a constant-power test (CPT). In addition, since O 2 breathing is used to hasten elimination of CO from the blood, we examined the effect of breathing O 2 following exposure to CO on cerebral and muscle oxygenation during a subsequent exercise test under CO conditions. Methods: Nine men participated in three trials: (i) 3-h air exposure followed by a control CPT, (ii) 1-h air and 2-h CO (18.9ppm) exposure succeeded by a CPT under CO conditions (CPT COA), and (iii) 2-h CO and 1-h 100% normobaric O 2 exposure followed by a CPT under CO conditions (CPT COB). All exercise tests were performed at 85% of peak power output to exhaustion. Oxygenated ($Δ$[O 2Hb]), deoxygenated ($Δ$[HHb]) and total ($Δ$[tHb]) haemoglobin in cerebral, intercostal and vastus lateralis muscles were monitored with near-infrared spectroscopy throughout the CPTs. Results: Performance time did not vary between trials. However, the vastus lateralis and intercostal $Δ$[O 2Hb] and $Δ$[tHb] were lower in CPT COA than in CPT. During the CPT COB, the intercostal $Δ$[O 2Hb] and $Δ$[tHb] were higher than in the CPT COA. There were no differences in cerebral oxygenation between the trials. Conclusion: Inspiration of 18.9ppm CO decreases oxygenation in the vastus lateralis and serratus anterior muscles, but does not affect performance. Breathing normobaric O 2 moderates the CO-induced reductions in muscle oxygenation, mainly in the intercostals, but does not affect endurance. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.