Patients with chronic obstructive pulmonary disease (COPD) have slowed pulmonary O₂ uptake (V̇o_2p) kinetics during exercise, which may stem from inadequate muscle O₂ delivery. However, it is currently unknown how COPD impacts the dynamic relationship between systemic and microvascular O₂ delivery to uptake during exercise. We tested the hypothesis that, along with slowed V̇o_2p kinetics, COPD patients have faster dynamics of muscle deoxygenation, but slower kinetics of cardiac output (Q̇t) following the onset of heavy-intensity exercise. We measured V̇o_2p, Q̇t (impedance cardiography), and muscle deoxygenation (near-infrared spectroscopy) during heavy-intensity exercise performed to the limit of tolerance by 10 patients with moderate-to-severe COPD and 11 age-matched sedentary controls. Variables were analyzed by standard nonlinear regression equations. Time to exercise intolerance was significantly ( P < 0.05) lower in patients and related to the kinetics of V̇o_2p ( r = −0.70; P < 0.05). Compared with controls, COPD patients displayed slower kinetics of V̇o_2p (42 ± 13 vs. 73 ± 24 s) and Q̇t (67 ± 11 vs. 96 ± 32 s), and faster overall kinetics of muscle deoxy-Hb (19.9 ± 2.4 vs. 16.5 ± 3.4 s). Consequently, the time constant ratio of O₂ uptake to mean response time of deoxy-Hb concentration was significantly greater in patients, suggesting a slower kinetics of microvascular O₂ delivery. In conclusion, our data show that patients with moderate-to-severe COPD have impaired central and peripheral cardiovascular adjustments following the onset of heavy-intensity exercise. These cardiocirculatory disturbances negatively impact the dynamic matching of O₂ delivery and utilization and may contribute to the slower V̇o_2p kinetics compared with age-matched controls.