Physical exercise increases free radical production in muscle. It is generally accepted that supplementation with antioxidant vitamins such as vitamin C is a good practice to prevent muscle damage during training. Free radicals not only cause damage, but also serve as signals to adapt cells to exercise. We wanted to test if quenching free radicals with antioxidants might hinder adaptations during training and be detrimental for training efficiency. Supplementation with vitamin C significantly decreases training efficiency in rats (measuring maximal running time). This might be, because vitamin C decreases the exercise-induced expression of key transcription factors involved in mitochondrial biogenesis (e.g. PGC-1, NRF-1 and mTFA) and of a marker of mitochondrial content such as citrate synthase. Moreover administration of vitamin C prevented the increase in the expression of antioxidant enzymes (e.g. superoxide dismutase or glutathione peroxidase). Exercise itself generates oxidative stress only when it is exhaustive. Moderate exercise generates controlled amounts of oxidants which do not damage cells but rather trigger useful cellular adaptations. We report here that by preventing these adaptations with oral antioxidants the training efficiency is decreased and, thus the common practice of taking antioxidant vitamins should be seriously questioned.