This study examined the relationship between acute cardiorespiratory and muscle oxygenation and blood volume changes during prolonged exercise. Eight healthy male volunteers (mean maximum oxygen uptake ([Formula: see text]O2max) = 41.6 ± 2.4 mL/kg/min) performed 60 min submaximal cycling at 50% [Formula: see text]O2max. Oxygen uptake ([Formula: see text]O2) was measured by indirect spirometry, cardiac output (CO) was estimated using a PortapresTM, and right vastus lateralis oxyhemoglobin/ myoglobin (oxyHb/Mb), deoxyhemoglobin/myoglobin (deoxyHb/Mb), and total hemoglobin/myoglobin (total Hb/Mb) were recorded using near-infrared spectroscopy (NIRS). After 40 min of exercise, there was a significant increase in [Formula: see text]O2 due to a significantly higher arteriovenous oxygen difference ((a - v)O2diff). After 30 min of exercise CO remained unchanged, but there was a significant decrease in stroke volume and a proportionate increase in heart rate, thus indicating the occurrence of cardiovascular drift. During the first few minutes of exercise, there was a decline in oxyHb/Mb and total Hb/Mb, whereas deoxyHb/Mb remained unchanged. Thereafter, oxyHb/Mb and total Hb/Mb increased systematically until the termination of exercise while deoxyHb/Mb declined. After 40 min of exercise, these changes were significantly different from the baseline values. There were no significant correlations between the changes in the NIRS variables and systemic [Formula: see text]O2 or mixed (a - v)O2diff during exercise. These results suggest that factors other than localized changes in muscle oxygenation and blood volume account for the increased [Formula: see text]O2 during prolonged submaximal exercise. Key words: near infrared spectroscopy, cardiovascular drift, systemic oxygen consumption.