We investigated the effect of hypoxic acclimatization per se, without any concomitant influence of strenuous physical activity on muscle and cerebral oxygenation. Eight healthy male subjects participated in a crossover-designed study. In random order, they conducted a 10-day normoxic (CON) and a 10-day hypoxic (EXP) confinement. Pre and post both CON and EXP confinements, subjects conducted two incremental-load cycling exercises to exhaustion; one under normoxic, and the other under hypoxic (FIO2=0.154) conditions. Oxygen uptake (V ̇ O 2), ventilation (V ̇ E), and relative changes in regional hemoglobin oxygenation ($Δ$([HbO2]) in the cerebral cortex and in the serratus anterior (SA) and vastus lateralis (VL) muscles were measured. No changes were observed in the CON confinement. Peak work rate and V ̇ O 2 peak were similar pre and post in the EXP confinement, whereas V ̇ E increased in the EXP post normoxic and hypoxic trials (P<0.05). The exercise-induced drop in VL $Δ$[HbO2] was less in the post- than pre-EXP trial by 4.0±0.4 and 4.2±0.6$μ$M during normoxic and hypoxic exercise, respectively. No major changes were observed in cerebral or SA oxygenation. These results demonstrate that a 10-day hypoxic exposure without any concomitant physical activity had no effect on normoxic or hypoxic V ̇ O 2 peak, despite the enhanced VL oxygenation. © 2013 John Wiley & Sons A/S.