BACKGROUND: Exercise training is essential for pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD), yet patient responsiveness varies widely. We previously observed metabolic disturbances in amino acids critical for muscle health-such as glutamate, glutamine, branched-chain amino acids (BCAAs), and taurine-in COPD patients after an endurance exercise session, possibly related to increased energy demands and oxidative stress. However, the impact of resistance exercise on these metabolic pathways remains unclear. METHODS: We measured plasma concentration, whole-body production (WBP), and intracellular production of glutamate, glutamine, BCAAs, and taurine using stable isotope pulse techniques in 24 COPD and 25 healthy older participants. Measurements were obtained before, and at 1 and 24 h after, a resistance exercise session. RESULTS: At baseline, COPD participants exhibited lower WBP of glutamine, taurine, and BCAAs compared to healthy participants (p <
0.05). Resistance exercise increased WBP of glutamate by 37-42 %, glutamine by 9-10 %, and intracellular glutamate production by 37-40 %, while decreasing WBP of taurine by 7 % (all p <
0.0001). These effects persisted at 24 h post-exercise (p <
0.05). Although WBP of BCAAs remained unchanged, plasma leucine and isoleucine levels decreased by 16 % and 13 %, respectively, in COPD participants post-exercise (p <
0.05). CONCLUSIONS: A single resistance exercise session alters glutamate-related metabolism for at least 24 h in healthy and COPD participants. A high BCAA clearance is likely required to rapidly upregulate glutamate production in COPD to meet increased energy demands, but this occurs at the cost of lowering plasma levels of BCAA necessary for muscle anabolism. CLINICAL TRIAL REGISTRY: Trial registration ClinicalTrials.gov: NCT02780219.