Objective: Examine the mediating role of diet in the relationship between volume and duration of sedentary time with cardiometabolic health in adolescents. Methods: Adolescents (12-19 years) participating in the 2003/04 and 2005/06 U.S. National Health and Nutrition Examination Survey (NHANES) were examined. Cardiometabolic health indicators were body mass index z-scores (zBMI) (n = 1,797) and metabolic syndrome (MetS) (n = 812). An ActiGraph hip-worn accelerometer was used to derive total sedentary time and usual sedentary bout duration. Dietary intake was assessed using two 24-hour dietary recalls. Mediation analyses were conducted to examine five dietary mediators [total energy intake, discretionary foods, sugar-sweetened beverages (SSB), fruits and vegetables, and dietary quality] of the relationship between total sedentary time and usual sedentary bout duration with zBMI and MetS. Results: Total sedentary time was inversely associated with zBMI (β = −1.33; 95% CI −2.53 to −0.13) but attenuated after adjusting for moderate-to-vigorous physical activity. No significant associations were observed between usual sedentary bout duration with zBMI or either sedentary measure with MetS. None of the five dietary variables mediated any of the relationships examined. Conclusions: Further studies are needed to explore associations of specific time periods (e.g., after school) and bout durations with both cardiometabolic health indicators and dietary behaviors.