Background: There is strong theoretical and empirical support for school connectedness as an important element of healthy youth development. The primary objective of this study was to replicate previous research identifying factors differentiating youth who do not feel connected to their schools in a sample of adolescents in Ontario, Canada. A secondary objective was to extend this work by assessing whether physical activity was an additional health behavior that differentiated youth who feel connected to their schools from those who do not. Methods: Data for this study were based on questionnaires from 2243 grade 7 to grade 12 students derived from the 2001 cycle of the Ontario Student Drug Use Survey. Logistic regression analysis was used to examine associations between physical activity, other health risk factors, and school disconnectedness. Results: The odds of feeling disconnected from their schools were substantially greater for female students who perceived their health or academic performance to be poor, engaged in no vigorous physical activity, reported 3 or more physician visits during the past year, and had low extracurricular involvement. None of the sociodemographic factors or substance use measures was significantly associated with school disconnectedness for any students. Conclusions: Our results highlight sex differences in how school disconnectedness is related to health-compromising behaviors such as physical inactivity. Further research is required to examine how boys and girls perceive, interpret, and internalize the school climate. Increasing school connectedness should be a consideration for academic administrators and health-promotion advocates. (Contains 2 tables and 1 figure.)