To determine the role of arterial O2 content on the mechanism of muscle O2 utilization, we studied the effect of 2, 11, and 20% carboxyhemoglobin (COHb) on O2 uptake (V̇O2), and CO2 output (V̇CO2) kinetics in response to 6 min of constant moderate- and heavy-intensity cycle exercise in 10 subjects. Increased COHb did not affect resting heart rate, V̇O2 or V̇CO2. Also, the COHb did not affect the asymptotic V̇O2 in response to exercise. However, V̇O2 and V̇CO2 kinetics were affected differently. The time constant (TC) of V̇O2 significantly increased with increased COHb for both moderate and heavy work intensities. V̇O2 TC was positively correlated with blood lactate. In contrast, V̇CO2 TC was negatively correlated with increased COHb for the moerate but unchanged for the heavy work intensity. The gas exchange ratio reflected a smaller increase in CO2 stores and faster V̇CO2 kinetics relative to V̇O2 with increased COHb. These changes can be explained by compensatory cardiac output (heart rate) increase in response to reduced arterial O2 content. The selective slowing of V̇O2 kinetics, with decreased blood O2 content and increased cardiac output, suggests that O2 is diffusion limited at the levels of exercise studied.