“Central” and “peripheral” limitations to oxidative metabolism during exercise were evaluated in 10 young males following a 35-day horizontal bed rest (BR). Incremental exercise (IE) and moderate- and heavy-intensity constant-load exercises (CLE) were carried out on a cycloergometer before and 1-2 days after BR. Pulmonary gas exchange, cardiac output (Q; by impedance cardiography), skeletal muscle (vastus lateralis), and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined. After BR, “peak” (values at exhaustion during IE) workload, peak O2 uptake (Vo2Peak), peak stroke volume, Qpeak, and peak skeletal muscle O2 extraction were decreased (-18, -18, -22, -19, and -33%, respectively). The gas exchange threshold was ∼60% of Vo2peak both before and after BR. At the highest workloads, brain oxygenation data suggest an increased O2 extraction, which was unaffected by BR. Vo2 kinetics during CLE (same percentage of peak workload before and after BR) were slower (time constant of the “fundamental” component: 31.1 ± 2.0 s before vs. 40.0 ± 2.2 s after BR); the amplitude of the “slow component” was unaffected by BR, thus it would be greater, after BR, at the same absolute workload. A more pronounced “overshoot” of skeletal muscle O 2 extraction during CLE was observed after BR, suggesting an impaired adjustment of skeletal muscle O2 delivery. The role of skeletal muscles in the impairment of oxidative metabolism during submaximal and maximal exercise after BR was identified. The reduced capacity of peak cardiovascular O2 delivery did not determine a “competition” for the available O2 between, skeletal muscles and brain. Copyright © 2010 the American Physiological Society.