OBJECTIVE: The objective of this study was to examine the influence of body weight and body composition on aspects of aerobic fitness. Our hypothesis was that increased body weight, specifically increased fat mass (FM), would not limit VO2max relative to fat-free mass (FFM), but would reduce maximal and sub-maximal VO2max relative to body weight. DESIGN: We used data from two ongoing studies. In Study 1 a cross-sectional analysis of 129 children across a wide spectrum of body composition was performed. In Study 2 we examined data from 31 overweight women before and after weight loss. METHODS: VO2max was measured using a treadmill test. Sub-maximal aerobic capacity was evaluated with respiratory exchange ratio (RER), heart-rate (HR), and oxygen uptake relative to VO2max at a given workload (%VO2max). Body composition was assessed using dual energy X-ray absorptiometry (DXA) (Study 1) and a four-compartment model (Study 2). RESULTS: In Study 1, FFM was the strongest determinant of VO2max (r=0.87; P<0.0001). After adjusting for FFM, there was no significant influence of FM on VO2max. After separating children into lean and obese sub-groups, absolute VO2max was significantly higher in the obese (1.24+/-0.27 vs 1.56+/-0.40) and VO2max relative to body weight was significantly lower (44.2+/-3.2 vs 32.0+/-4.1 ml/(kg-min)), whereas there was no significant difference when expressed relative to FFM (57.9+/-5.8 vs 59.2+/-4.9 ml/(kgFFM-min)). Sub-maximal aerobic capacity was significantly lower in the obese children, as indicated by a higher HR and %VO2max; time to exhaustion was significantly lower in the obese children (15.3+/-2.9 vs 11.1+/-2.1 min). In Study 2, FFM was also the strongest determinant of VO2max before and after weight loss. The relationship between VO2max and FFM was identical before and after weight loss so that VO2max relative to FFM was identical before and after weight loss (43.8+/-4.9 vs 45.5+/-6.4 ml/(kgFFM-min)). However, sub-maximal aerobic capacity was lower in the obese state, as indicated by a significantly higher RER (0.85+/-0.06 vs 0.79+/-0.05), HR (124+/-14 vs 102+/-11 bpm), and %VO2max (44% vs 36%). CONCLUSION: The major influence of body weight on VO2max is explained by FFM; FM does not have any effect on VO2max. Fatness and excess body weight do not necessarily imply a reduced ability to maximally consume oxygen, but excess fatness does have a detrimental effect on submaximal aerobic capacity. Thus, fatness and VO2max should be considered independent entities.