Aim This guideline is concerned with measures to prevent and control the transmission of SARS-CoV-2 in primary and secondary schools, addressing school premises and all school-related activities, as well as routes to and from school. Methods This evidence- and consensus-based S3 guideline was registered with the AWMF and developed by guideline panelists representing a broad range of scientific societies across multiple disciplines, public health and educational institutions, as well as associations of those directly affected, notably teachers, students and parents. Recommendations This guideline contains recommendations on hybrid learning and cohorting of classes or students, wearing masks, measures on the way to school and in class, managing suspected cases and contact persons in schools, options for reducing aerosol concentrations in classrooms and testing strategies. In developing these, the guideline panel considered: balance of health benefits and harms, legal aspects, socio-cultural acceptability, health equity and non-discrimination, social and ecological consequences, financial and economic consequences and feasibility.