In this retrospective cohort study involving 614 secondary school students, the likelihood of becoming infected with SARS-CoV-2 in schools with different focus (sports focus vs. general branch; the only difference in the sports focus school was that PE was allowed at all times without restrictions) and different prevailing restrictions were compared. A significantly higher likelihood of infection with SARS-CoV-2 was found in sports classes during the period with a strict FFP-2 mask requirement compared to general branch classes (for Delta from November 2021 to December 2021, and for Omicron from January 2022 to February 2022). The higher likelihood of infection was observed both during the Delta and the Omicron wave. After the relaxation of the mitigation measures, however, students in general branch classes showed a clear "catch-up" of infections, leading to a higher incidence of infections during this phase. By the end of the observation period (30 April 2022), only a small difference in cumulative SARS-CoV-2 infection rates ( = 0.037, φ = 0.09) was detected between classes with a sports focus and those without a sports focus. The results suggest that SARS-CoV-2 transmission can be reduced in school classes by mandatory FFP-2 mask use. In many cases, however, infection appears to be postponed rather than avoided.