We tested the hypothesis that, after bed rest, maximal oxygen consumption ( VO₂max ) decreases more upright than supine, because of adequate cardiovascular response supine, but not upright. On 9 subjects, we determined VO₂max and maximal cardiac output (Q ) upright and supine, before and after (reambulation day upright, the following day supine) 35-day bed rest, by classical steady state protocol. Oxygen consumption, heart rate (f(H)) and stroke volume (Q(st)) were measured by a metabolic cart, electrocardiography and Modelflow from pulse pressure profiles, respectively. We computed Q as f(H) times Q(st), and systemic oxygen flow ( QaO₂) as Q. times arterial oxygen concentration, obtained after haemoglobin and arterial oxygen saturation measurements. Before bed rest, all parameters at maximal exercise were similar upright and supine. After bed rest, VO₂max was lower (p<0.05) than before, both upright (-38.6%) and supine (-17.0%), being 30.8% higher supine than upright. Maximal Q(st) decreased upright (-44.3%), but not supine (+3.7%), being 98.9% higher supine than upright. Maximal Q decreased upright (-45.1%), but not supine (+9.0%), being higher supine than upright (+98.4%). Maximal QaO₂ decreased upright (-37.8%), but not supine (+14.8%), being higher (+74.8%) upright than supine. After bed rest, the cardiovascular response (i) did not affect VO₂max supine, (ii) partially explained the VO₂max decrease upright, and (iii) caused the VO₂max differences between postures. We speculate that impaired peripheral oxygen transfer and/or utilisation may explain the VO₂max decrease supine and the fraction of VO₂max decrease upright unexplained by cardiovascular responses.