Resting energy expenditure (REE) in adults is influenced by fat-free mass (FFM) and fat mass (FM), and is significantly higher in men than in women. There are limited data, however, on the physiologic determinants of REE in children. We therefore measured REE in 113 prepubertal children (39 white girls, 41 white boys, 21 Mohawk girls, and 12 Mohawk boys), 3.9 to 7.8 years of age, representing a wide range of body weight (14.7 to 34.0 kg), height (0.97 to 1.30 m), FFM (10.3 to 25.0 kg), and FM (1.7 to 13.7 kg; 9.4% to 40.3%). The REE was measured in duplicate by indirect calorimetry (range, 830 to 1405 kcal/day) while the children were in a postprandial state and viewing a cartoon film. The FM and FFM values were determined by bioelectrical resistance by means of the Kushner equation. In stepwise regression analysis, the combination of FFM (p < 0.001; partial r = 0.77), sex (p = 0.001; partial r = 0.12), and FM (p = 0.01; partial r = 0.16) explained 63% of the variation in REE. The regression coefficients were 31.9 kcal/kg FFM, 53 kcal for boys, 0 for girls, and 13 kcal/kg FM. Mohawk background, age, fat distribution, heart rate, and physical activity were not independently associated with REE. After REE was adjusted for the aforementioned significant factors, there were no significant correlations with parental factors (body composition, physical activity, age, and REE) other than normalized maternal REE (r = 0.19; p = 0.05). We conclude that the effects of FFM, sex, and FM on REE in children are similar to those in adults. The higher REE in young boys suggests that the previously reported higher REE in adult men cannot be explained entirely by differences in sex hormones. Finally, our data do not support the hypothesis that REE in children is negatively influenced by obesity in children or in parents.