To examine the relative association of physical activity, cardiorespiratroy fitness (CRF), and adiposity with risk for metabolic disease in prepubescent children. Forty-six prepubescent children (age, 9.4 ± 1.7 years; 24 males) were assessed for adiposity (%fat) via dual-energy X-ray absorptiometry, CRF with a peak graded exercise test, and physical activity using pedometers. Metabolic disease risk was assessed by a composite score of the following factors: waist circumference (WC), mean arterial pressure (MAP), triacylglycerol (TAG), total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C ratio), glucose, and insulin. Adiposity was correlated with metabolic disease risk score, as well as homeostasis model assessment of insulin resistance (HOMA-IR), TAG, TC/HDL-C ratio, WC, insulin, and MAP (r range = 0.33 to 0.95, all p < 0.05). Physical activity was negatively associated with metabolic disease risk score, as well as HOMA-IR, TAG, WC, insulin, and MAP (r range = -0.32 to -0.49, all p < 0.05). CRF was inversely associated with metabolic disease risk score and HOMA-IR, TAG, TC/HDL-C ratio, WC, insulin, and MAP (r range = -0.32 to -0.63, all p < 0.05). Compared across fitness-physical activity and fatness groups, the low-fit-high-fat and the low-activity-high-fat groups had higher metabolic risk scores than both low-fat groups. Regression analyses revealed sexual maturity (β = 0.27, p = 0.044) and %fat (β = 0.49, p = 0.005) were the only independent predictors of metabolic disease risk score, explaining 4.7% and 9.5% of the variance, respectively. Adiposity appears to be an influential factor for metabolic disease risk in prepubescent children, and fitness is protective against metabolic disease risk in the presence of high levels of adiposity.