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A single-center randomized, controlled cross-over exercise intervention in 20 women willing to reduce weight (20–40 y, BMI: 27.4 ± 2.1), with the aim to examine potential benefits for weight loss under normal (N-Ox: 20.9%) and mildly reduced (R-Ox: 17.0%) normobaric oxygen in an “Altitude Simulation Chamber”. O₂ consumption (<i>V</i>O₂), CO₂ production (<i>V</i>CO₂), blood oxygen saturation (SaO₂), blood glucose and lactate (mM) were studied before, during and after cycling for 22 min at a mean personalized workload of 54.2 ± 11.7 watts, about 40% of <i>V</i>O₂max. Despite lower absolute SaO₂ values and a greater decline from rest to exercise under R-Ox (time x treatment interaction <i>p</i> < 0.01), <i>V</i>O₂ did not differ from N-Ox (time x treatment interaction <i>p</i> = 0.178). Average net <i>V</i>O₂, 13.8 mL O₂ per watt, reflected fairly normal aerobic cycling, irrespective of O₂ regime. The Respiratory Exchange Ratio (RER; <i>V</i>O₂/<i>V</i>CO₂), 0.83 at rest, increased for both treatments to a ratio close to or beyond unity during and directly after exercise (treatment effect <i>p</i> = 0.407). The tendency of cycling for weight loss to clear carbohydrates rather than fat, irrespective of normal or mildly reduced normobaric oxygen, is discussed as a lactate-mediated and phenotype-specific consequence of apparent anaerobic glycolysis with adverse perspectives for weight loss and metabolic health.