Insulin resistance is believed to be the process underlying type 2 diabetes and premature cardiovascular disease. We have established that a relation between body mass and insulin resistance calculated by homeostasis model assessment (HOMA-IR) exists by 5 y of age in contemporary UK children. Resting energy expenditure (REE) is variable among individuals and is one of many factors controlling body mass. The objective was to investigate the relations between REE, body mass, and HOMA-IR in young children. EarlyBird is a nonintervention prospective cohort study of 307 healthy 5-y-olds that asks the question: Which children develop insulin resistance and why? REE by indirect calorimetry and HOMA-IR were measured in addition to total body mass, fat-free mass (FFM) by bioimpedance, body mass index (BMI; in kg/m(2)), and skinfold thickness when the mean age of the cohort was 5.9 +/- 0.2 y. Whereas the BMI of the boys was lower than that of the girls (x +/- SD: boys, 15.9 +/- 1.9; girls, 16.5 +/- 1.9; P = 0.03), their REE was higher by 6% (x +/- SD: 4724 +/- 615 compared with 4469 +/- 531 kJ/d; P = 0.002). This difference persisted after adjustment for FFM and other anthropometric variables (P = 0.04). In boys, there was a weak, although significant, inverse correlation between REE and HOMA-IR, independent of fat mass and FFM (boys: r = -0.21, P = 0.03; girls: r = 0.12, P = 0.34). There is a sex difference in REE at 6 y of age that cannot be explained by body composition. The difference appears to be intrinsic, and its contribution to sex differences in adiposity and HOMA-IR in children merits further exploration.