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Obesity is a pediatric epidemic that is more prevalent in children with developmental disabilities. We hypothesize that soy protein-based diets increase weight gain and alter neurobehavioral outcomes. Our objective herein was to test matched casein- and soy protein-based purified ingredient diets in a mouse model of fragile X syndrome, <i>Fmr1^KO</i> mice. The experimental methods included assessment of growth; 24-7 activity levels; motor coordination; learning and memory; blood-based amino acid, phytoestrogen and glucose levels; and organ weights. The primary outcome measure was body weight. We find increased body weight in male <i>Fmr1^KO</i> from postnatal day 6 (P6) to P224, male wild type (WT) from P32–P39, female <i>Fmr1^KO</i> from P6–P18 and P168–P224, and female <i>Fmr1^HET</i> from P9–P18 as a function of soy. Activity at the beginning of the light and dark cycles increased in female <i>Fmr1^HET</i> and <i>Fmr1^KO</i> mice fed soy. We did not find significant differences in rotarod or passive avoidance behavior as a function of genotype or diet. Several blood-based amino acids and phytoestrogens were significantly altered in response to soy. Liver weight was increased in WT and adipose tissue in <i>Fmr1^KO</i> mice fed soy. Activity levels at the beginning of the light cycle and testes weight were greater in <i>Fmr1^KO</i> versus WT males irrespective of diet. DEXA analysis at 8-months-old indicated increased fat mass and total body area in <i>Fmr1^KO</i> females and lean mass and bone mineral density in <i>Fmr1^KO</i> males fed soy. Overall, dietary consumption of soy protein isolate by C57BL/6J mice caused increased growth, which could be attributed to increased lean mass in males and fat mass in females. There were sex-specific differences with more pronounced effects in <i>Fmr1^KO</i> versus WT and in males versus females.