Background Muscle wasting is frequent in chronic obstructive lung disease (COPD) and associated with low branched-chain amino acids (BCAA). We hypothesized that BCAA supplementation could potentiate the effect of a pulmonary rehabilitation program (PRP) by inducing muscular change. Materials and methods Sixty COPD patients (GOLD 2–3) were involved in an ambulatory 4-week PRP either with BCAA oral daily supplementation or placebo daily supplementation in a randomized double-blind design. Maximal exercise test including quadriceps oxygenation measurements, functional exercise test, muscle strength, lung function tests, body composition, dyspnea and quality of life were assessed before and after PRP. Results Fifty-four patients (64.9 ± 8.3 years) completed the protocol. In both groups, maximal exercise capacity, functional and muscle performances, quality of life and dyspnea were improved after 4-week PRP (p ≤ 0.01). Changes in muscle oxygenation during the maximal exercise and recovery period were not modified after 4-week PRP in BCAA group. Contrarily, in the placebo group the muscle oxygenation kinetic of recovery was slowed down after PRP. Conclusion This study demonstrated that a 4-week PRP with BCAA supplementation is not more beneficial than PRP alone for patients. A longer duration of supplementation or a more precise targeting of patients would need to be investigated to validate an effect on muscle recovery and to demonstrate other beneficial effects.