Background Obesity prevalence is increased in children with developmental disabilities, specifically in children with spina bifida and Down syndrome. Energy expenditure, a critical aspect of weight management, has been extensively studied in the typically developing population, but not adequately studied in children with developmental disabilities. Objective Determine energy expenditure, fat-free mass and body fat percentile and the impact of these findings on recommended caloric intake in children with spina bifida and Down syndrome. Methods/Measures This pilot study included 36 children, 18 with spina bifida, 9 with Down syndrome and 9 typically developing children. Half of the children with spina bifida were non-ambulatory. Doubly labeled water was used to measure energy expenditure and body composition. Descriptive statistics described the sample and MANOVA and ANOVA methods were used to evaluate differences between groups. Results Energy expenditure was significantly less for children with spina bifida who primarily used a wheelchair (p = .001) and children with Down syndrome (p = .041) when compared to children without a disability when adjusted for fat-free mass. However, no significant difference was detected in children with spina bifida who ambulated without assistance (p = .072). Conclusions Children with spina bifida and Down syndrome have a significantly decreased energy expenditure which directly impacts recommended caloric intake. No significant difference was detected for children with spina bifida who ambulated, although the small sample size of this pilot study may have limited these findings. Validating these results in a larger study is integral to supporting successful weight management of these children