Maximal oxygen uptake and maximal work rate decreased along with fractional inspired oxygen due to decreasing convective oxygen transport, whereas diffusive oxygen conductance was not altered by FIO2.

At submaximal intensities alterations to muscle oxygenation develop at lower work rates in hypoxia, but at maximal exercise, muscle oxygenation is altered to a similar extent in hypoxia and normoxia compared to resting levels. Crucially, similar values are reached at a lower work rate in hypoxia.

Central and peripheral compensatory mechanisms maintain oxygen uptake at submaximal intensities despite alterd fractional inspired oxygen.

We combined non-invasive methodology with the gold standard theoretical framework of the determinants of VO2max and characterized how the integrated interplay of the central and peripheral components of O2 pathway determine responses to acute whole-body exercise under conditions of varied FIO2.