An emerging body of evidence suggests that sedentary behavior (SB) is an independent risk factor for cardiometabolic disease. Recent data suggest that multi-domain SB has detrimental associations with BMI, waist circumference (WC), and nonadiposity-related (total cholesterol, high density lipoprotein cholesterol (HDL-C), systolic (SBP) and diastolic (DBP) blood pressure) cardiometabolic risk markers. The aim of this cross-sectional study was to examine the extent to which the associations between SB and nonadiposity-related cardiometabolic risk markers are explained by adiposity markers. Subjects were 5,067 Health Survey for England (HSE) 2008 respondents (2,552 men) aged 16-65 years. The measurements protocol involved self-reports of television time, other recreational sitting, occupational sitting/standing, physical activity and objective measures of weight, height, WC, total cholesterol, HDL cholesterol, SBP, and DBP. BMI or WC adjustments of the multivariable models looking at the associations between SB and nonadiposity markers attenuated all associations towards the null. Using established logistic regression-based algorithms we calculated that a large percentage of the associations between SB time and nonadiposity risk factors is explained by BMI or WC (range: 27.3-95.9%). Future longitudinal studies should further examine the mediatory role of adiposity in explaining the associations between SB and cardiometabolic risk.