This study examined the relationship between the acute cardiorespiratory and muscleoxygenation/blood volume changes during prolonged exercise. Eight healthy male volunteers (mean VO2max = 41.6 ± 2.4 ml/kg/min) performed 60 minutes submaximal cycling at 500f VO2max. Oxygen uptake (VO2) was measured by indirect spirometry, cardiac output (CO) was estimated via Portapres, 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. After 40 minutes of exercise, there was a significant increase in VO2 due to a significantly higher (a – v)O2diff. After 30 mins of exercise CO was unchanged, but there was a significant decrease in stroke volume and a proportionate increase in heart rate indicating the occurrence of cardiovascular drift. During the first few minutes of exercise, there was a decline in OxyHb/Mb and Total Hb/Mb while DeoxyHb/Mb remained unchanged. Thereafter OxyHb/Mb and Total Hb/Mb increased systematically until the termination of exercise while DeoxyHb/Mb declined. After 40 minutes of exercise, these changes were significantly different from the baselines values. There were no significant correlations between the changes in the NIRS variables and systemic VO2 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 VO2 during prolonged submaximal exercise.