Data was collected from 25,060 Canadian students in grades 9 through 12 from 76 secondary schools in Ontario. Low active-high sedentary boys were 60% more likely to be overweight than high active-low sedentary boys. Girls who were low active-high sedentary had more than double the risc of high active-low sedentary girls to be overweight. Sedentary behavior may moderate the relationship between physical activity and overweight. Developing a better understanding of sedentary behavior in relation to physical activity and overweight is critical for preventing and reducing overweight among youth.