Objective: To examine associations of volumes and bouts of sedentary behavior (SED) and moderate-to-vigorous physical activity (MVPA) with individual and clustered cardio-metabolic outcomes in overweight/obese children. Methods: Cross-sectional data from 120 overweight/obese children (8.3 ± 1.1 years, 62% girls, 74% obese) with SED and MVPA assessed using accelerometry. Children were categorized into quartiles of mean bouts per day of SED (10, 20, and 30 min) and MVPA (5, 10, and 15 min). Associations with triglycerides, HDL cholesterol, glucose, insulin, systolic/diastolic blood pressure, and clustered cardio-metabolic risk (cMet) were examined using linear regression, adjusted for confounders. Results: Independent of MVPA, SED volume was inversely associated with HDL cholesterol (β [95% CI] = −0.29 [−0.52, −0.05]). MVPA volume was inversely associated with diastolic blood pressure, independent of SED (β=−0.22 [−0.44, −0.001]), and cMet (β=−0.19 [−0.36, −0.01]) although not after adjustment for SED (β=−0.14 [−0.33, 0.06]). Independent of MVPA and SED volumes, participants in the highest quartile of 30 min bouts per day of SED had 12% lower HDL cholesterol than those in the lowest quartile (d = 0.53, P = 0.046, Ptrend = 0.11). Conclusions: In addition to increasing MVPA, targeting reduced SED and limiting bouts of SED to <30 min may contribute to improved HDL cholesterol levels and cardio-metabolic health in overweight/obese children.