To determine if a 36-h fast affects the central and peripheral components of VO2 during submaximal exercise and peak oxygen uptake (VO2 peak), 10 physically healthy males exercised first for 10 min at approximately 60% of their VO2 peak and then to fatigue. Their cardiovascular responses were compared with those of 10 physically healthy controls (males) who were individually matched by VO2 peak values. Fasting had no significant effect on the central (heart rate, HR; stroke volume, SV; cardiac output, Q) and peripheral (arteriovenous oxygen content difference, a-vO2 diff.) components of VO2 during submaximal exercise. The respiratory exchange ratio (RER) during submaximal exercise was significantly decreased in the fasted subjects. Based on the RER, fasting altered substrate utilization of the muscle and thereby increased the contribution of fat during submaximal exercise. Fasting had no significant effect on VO2 peak, HR or O2 pulse, but RER was significantly lower during incremental exercise to fatigue. These results demonstrate that VO2 during submaximal exercise in fasted subjects is achieved by similar central and peripheral responses as found in non-fasted subjects, and that fasting does not reduce VO2 peak.