Technical Abstract: Genome-wide scans were conducted in a search for genetic locations linked to energy expenditure and substrate oxidation in children. Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La Familia Study, which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. A respiratory calorimeter was used to measure 24-h total energy expenditure (TEE), basal metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient (24RQ), basal metabolic respiratory quotient (BMRQ), and sleep respiratory quotient (SRQ). Protein, fat, and carbohydrate oxidation (PROOX, FATOX, and CHOOX, respectively) were also estimated. All participants were genotyped for 384 single tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR was used to perform the genetic linkage analyses. Significant linkage for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the odds (LOD) score of 4.0. SMR, BMRQ, and PROOX were associated with loci on chromosome 18, 17, and 9, respectively, with LOD scores of 4.88, 3.17, and 4.55, respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was observed for CHOOX and FATOX. Several candidate genes were found in the above chromosomal regions, including leptin receptor (LEPR). Regions on chromosomes 1, 9, 17, and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents.