The aims of the present study were to examine possible effects of age and sex on energy expenditure independent of differences in body composition, and to develop prediction equations for individual estimation of energy expenditure. The study is based on 235 female and 78 male subjects ranging in age from 15 to 64 y and with body mass indexes (in kg/m2) ranging from 16.9 to 50.5. Basal metabolic rate (BMR), sleeping energy expenditure, and 24-h energy expenditure were measured with standardized protocols by indirect calorimetry in respiratory chambers. Anthropometric data were also recorded. Spontaneous physical activity (SPA) was estimated by a radar system during the chamber stay. About 90% of the variation in 24-b energy expenditure could be explained by differences in fat-free mass, fat mass, SPA, and duration of exercise (SEM: 526 kJ/d), whereas age and sex did not contribute significantly. When comparing energy expenditure adjusted for body composition and activity between two age groups (20-30 y, n = 98 and 50-65 y, n = 39), BMR was 4.6% lower in the older group (P = 0.04) and there was a tendency toward a lower sleeping energy expenditure in the older group (P = 0.06). No sex difference in any energy expenditure measurement could be found after differences in body composition and activity were taken into account. In conclusion, no sex effect and no linear decrease in energy expenditure was found with increased age and the middle-aged subjects had lower BMR than younger subjects independent of body size, body composition and activity.