AbstractObjectiveThe contribution of body composition to sex differences in strong prognostic cardiorespiratory variables remains unresolved. This study aimed to elucidate whether body composition determines sex differences in cardiac and oxygen (O₂) uptake responses to incremental exercise.MethodsHealthy, moderately active women and men (n = 60, age = 60.7 [12.3] years) matched by age and cardiorespiratory fitness were included. Body composition was determined via dual‐energy x‐ray absorptiometry. Transthoracic echocardiography and O₂ uptake were assessed at rest and throughout incremental exercise with established methods. Major cardiac and pulmonary outcomes were normalized by body surface area (BSA), total lean body mass (LBM), or leg LBM.ResultsWomen presented with smaller anthropometrical indices (height, weight, BSA) and LBM compared with men (p < 0.001). Peak exercise cardiac dimensions and output (i.e., peak cardiac outout [Q_peak]), commonly normalized by BSA, were reduced in women relative to men (p ≤ 0.019). Cardiac sex differences were abolished after normalization by total or leg LBM (p ≥ 0.115). Strong linear relationships of total and leg LBM with Q_peak and peak oxygen uptake were detected exclusively in women (r ≥ 0.53, p ≤ 0.003), independent of body fat percentage.ConclusionsTotal and leg LBM stand out as strong independent determinants of cardiac and aerobic capacities in women, regardless of body fat percentage, relationships that are not present in age‐ and fitness‐matched men.