PurposeThis study explores the impacts of school closures during the COVID-19 pandemic on the domains of adolescent well-being from the UN H6+ framework, reported by health and educational professionals worldwide.MethodsSemistructured individual online interviews were conducted in six languages during the second wave of the COVID-19 pandemic (March–December 2021) with health and education professionals who volunteered for follow-up after participating in an anonymous online survey. The UN H6+ 5-domain conceptual framework of adolescent well-being was used as a framework for the directed content analysis of the combined interview dataset.ResultsA total of 60 interviews—translated into English—were analyzed from 38 education and 22 health professionals in 28 countries/territories. Participant reports showed impacts on all five adolescent well-being domains, but mainly domain 1 (good health and nutrition), domain 3 (safety and a supportive environment) and domain 4 (learning, competence, education, skills, and employability). Reflections of 2-connectedness and 5-agency were also present. Their reports included mainly negative impacts, but also some positive insights to take forward.DiscussionPolicymakers must recognize impacts of school closures during the pandemic on multiple domains of adolescent well-being and the potential for widening inequalities. Schools play a critical mitigating role that goes beyond education. The call to action for the adolescent health community is to recognize and address ongoing potential long-term impacts on well-being and inequalities in their everyday practice. It is also important to advocate locally, nationally, and globally for careful consideration of the consequences of school closures in future health crises.