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Mental health among children and adolescents is a growing national concern and schools have taken center stage in efforts to prevent problems and promote wellness. Although research and policymakers support the integration of mental health services into the schools, there is limited agreement on the ways to package or combine existing supports to achieve prevention-oriented goals. Positive Behavioral Interventions and Supports (PBIS) and Social Emotional Learning (SEL) are 2 of the most widely adopted, evidence-based approaches that have been advocated to address student mental health. These universal prevention approaches, however, stem from different theoretical camps and are often advocated and implemented apart from one another. The purpose of this study was to examine the independent and combined effects of PBIS and SEL on student mental health outcomes. A quasi-randomized control design at the classroom level was used to make comparisons across 4 conditions: business-as-usual (BAU), PBIS alone, SEL alone, and COMBO condition with regard to their acceptability to teachers, integrity of program delivery, and student outcomes. As predicted, the COMBO condition produced significantly greater improvements in overall mental health and reductions in externalizing behaviors when compared to all other conditions. The results also indicated that the PBIS- and SEL-only conditions were both able to produce significant improvements in overall mental health functioning as compared with the BAU control. The implications of an integrated approach for school-based universal prevention and directions for future research are discussed.