Determining total energy expenditure (TEE) and its components in children treated with home parenteral nutrition (CHPN) under free-living conditions is an important consideration in the assessment of energy requirements and the maintenance of health. The aim of this study was to assess TEE and physical activity in CHPN. Eleven CHPN (three girls and eight boys; median age, 6.0 y; range, 4.5-15.0 y) were compared with 11 healthy children (three girls and eight boys; median age, 6.0 y, range, 4.5-14.0 y) after pairing for sex, age, and weight. Underlying diseases included chronic intractable diarrhea (n = 5), short bowel syndrome (n = 3), and intestinal dysmotility (n = 3). None of these children had inflammatory disease or recent infection when studied. Fat-free mass (FFM), measured by body impedance analysis, fat mass (FM), measured by skinfold thickness, and energy intake were similar between the two groups, suggesting that CHPN had normal body composition and energy intake. Resting energy expenditure (REE), measured by indirect calorimetry, and TEE, assessed by a technique using 24-h heart-rate monitoring calibrated against indirect calorimetry and physical activity using a triaxial accelerometer, were simultaneously recorded and were also similar in the two groups. Sleeping energy expenditure (SEE), expressed per kilogram of FFM, was significantly greater in the CHPN group (median, 0.15; range, 0.10-0.23 kJ/min/kg FFM versus median, 0.12; range, 0.09-0.21 kJ/min/kg FFM for controls; p < 0.05, Wilcoxon rank test). These findings were explained by the high correlation between the energy flow infused by parenteral nutrition and sleeping energy expenditure (p < 0.05, Spearman test) and also-diet induced thermogenesis (p < 0.05 Spearman test). These results suggest that the energy requirements of children on long-term home parenteral nutrition programs do not differ from controls and that cyclic parenteral nutrition does not interfere with physical activity.