Objective: We tested the hypothesis that systemic hypoxia would suppress MPS at rest and blunt responses to RE. Methods: Seven healthy men (~20 y, ~24 kg.m^-2) participated in a crossover study in which MPS responses to RE under atmospheric conditions and normobaric hypoxia (inspired air, 12.5% O₂) were determined. On study days (>3 mo apart), antecubital veins were cannulated to permit tracer infusions and blood sampling, before subjects performed unilateral RE comprising 8 × 6 repetitions at 70% 1-Repetition Maximum. Immediately after RE a muscle biopsy was taken and a primed, constant IV infusion of 1,2- [¹³C₂]leucine (0.75 mg.kg^-1) was maintained for 2.5 h, after which quadriceps biopsies were taken from both legs. Trial protocols were identical except that in the hypoxia trial, subjects breathed 12.5% O₂ for 1 h before RE and for a further 2.5 h. Oxygen partial pressure saturation (SpO₂) was recorded using a pulse oximeter and MPS measured as incorporation of 1,2-[¹³C₂] leucine into myofibrillar proteins using gas chromatography-combustion-isotope-ratio mass- spectrometry. Data were analyzed by paired ANOVA and Pearson's correlation. Results: Peak force was not different between trials (629±63 vs. 613±60 N). Throughout normoxia SpO₂ was constant (97-98%). In contrast, SpO₂ fell within 10 min in hypoxia trials (86.4±1.7%) and remained depressed throughout (mean 82.7±0.5%). MPS increased significantly 2.5 h after RE in normoxia 0.033 (0.022-0.052) vs. 0.104 (0.069-0.149) %h.^-1 (median (95% CI); P<0.01) but was unaltered in the resting leg or the exercised leg after 3.5 h of hypoxia 0.043 (0.029-0.059) vs. 0.06 (0.03-0.146) %h.^-1 (median (95% CI)). The extent of blunting in MPS responses to RE was correlated with the extant SpO₂ (r²= 0.48; P=0.04). Conclusion: Systemic hypoxia blunts the expected increases in MPS typically seen after RE.