BACKGROUND Respiratory muscle unloading during exercise could improve locomotor muscle oxygenation by increasing oxygen delivery (higher cardiac output and/or arterial oxygen content) in patients with chronic obstructive pulmonary disease (COPD). METHODS Sixteen non-hypoxaemic men (forced expiratory volume in 1 s 42.2 (13.9)% predicted) undertook, on different days, two constant work rate (70-80% peak) exercise tests receiving proportional assisted ventilation (PAV) or sham ventilation. Relative changes (Delta%) in deoxyhaemoglobin (HHb), oxyhaemoglobin (O(2)Hb), tissue oxygenation index (TOI) and total haemoglobin (Hb(tot)) in the vastus lateralis muscle were measured by near-infrared spectroscopy. In order to estimate oxygen delivery (Do(2)est, l/min), cardiac output and oxygen saturation (Spo(2)) were continuously monitored by impedance cardiography and pulse oximetry, respectively. RESULTS Exercise tolerance (Tlim) and oxygen uptake were increased with PAV compared with sham ventilation. In contrast, end-exercise blood lactate/Tlim and leg effort/Tlim ratios were lower with PAV (p<0.05). There were no between-treatment differences in cardiac output and Spo(2) either at submaximal exercise or at Tlim (ie, Do(2)est remained unchanged with PAV; p>0.05). Leg muscle oxygenation, however, was significantly enhanced with PAV as the exercise-related decrease in Delta(O(2)Hb)% was lessened and TOI was improved; moreover, Delta(Hb(tot))%, an index of local blood volume, was increased compared with sham ventilation (p<0.01). CONCLUSIONS Respiratory muscle unloading during high-intensity exercise can improve peripheral muscle oxygenation despite unaltered systemic Do(2 )in patients with advanced COPD. These findings might indicate that a fraction of the available cardiac output had been redirected from ventilatory to appendicular muscles as a consequence of respiratory muscle unloading.