To determine the associations between cardiorespiratory fitness (CRF) and fatness (overweight-obesity) with cardiometabolic disease risk among preadolescent children. This cross-sectional study recruited 392 children (50% female, 8-10 years of age). Overweight-obesity was classified according to 2007 World Health Organization criteria for body mass index. High CRF was categorized as a maximum oxygen uptake, determined using a shuttle run test, exceeding 35 mL·kg-1·minute-1 in girls and 42 mL·kg-1·minute-1 in boys. Eleven traditional and novel cardiometabolic risk factors were measured including lipids, glucose, glycated hemoglobin, peripheral and central blood pressure, and arterial wave reflection. Factor analysis identified underlying cardiometabolic disease risk factors and a cardiometabolic disease risk summary score. Two-way analysis of covariance determined the associations between CRF and fatness with cardiometabolic disease risk factors. Factor analysis revealed four underlying factors: blood pressure, cholesterol, vascular health, and carbohydrate-metabolism. Only CRF was significantly (P = .001) associated with the blood pressure factor. Only fatness associated with vascular health (P = .010) and carbohydrate metabolism (P = .005) factors. For the cardiometabolic disease risk summary score, there was an interaction effect. High CRF was associated with decreased cardiometabolic disease risk in overweight-obese but not normal weight children (P = .006). Conversely, high fatness was associated with increased cardiometabolic disease risk in low fit but not high fit children (P < .001). In preadolescent children, CRF and fatness explain different components of cardiometabolic disease risk. However, high CRF may moderate the relationship between fatness and cardiometabolic disease risk. ACTRN 12614000433606.