The relationship between cardiac output (CardOut) and oxygen consumption (V_o2 ) during exercise has generally assumed to be linear. To test this assumption, we studied 72 healthy subjects using graded, 2-min cycle-ergometry exercise test to maximum while measuring gas exchange continuously and CardOut at the end of each stage, the latter using an open-circuit gas technique. Data for V_o2 and CardOut at each stage were fit to a quadratic expression y= a + b ^. + c ^. V_o2² and statistical significance of the quadratic "c" term was determined in each subject. Subjects were divided into two groups: those with statistically significant negative quadratic term ("negative curvature group", N=25) and those with either non-significant quadratic term or "c" significantly >0 ("non-negative curvature group", N=47, 2 with c significantly>0). We found the negative curvature group had significantly higher V_o2 /kg (median 37.9 vs 32.4ml/min/kg, P=0.03) higher resting stroke volume (SV, median 77 vs 60ml, P=0.04), lower resting HR (median 72 vs 82, P=0.04), and higher tissue oxygen extraction at maximal exercise (17.1 ± 2.2 vs 15.5 ± 2.1ml/100ml, P<0.01), with tendencies for higher maximal CardOut and SV. We found the HR vs V_o2 relationship to be negatively curved, with negative curvature in HR associated with negative curvature in CardOut (P< 0.05), suggesting the curvature in the CardOut vs V_o2 relationship was secondary to curvature in HR vs V_o2. We conclude the CardOut vs V_o2 relationship is not always linear, and negative curvature in the relationship is associated with higher fitness levels in normal, non-elite-athletic subjects.