The role that in-person schooling contributes to community incidence of SARS-CoV-2 infections and deaths remains unknown. We conducted an event study evaluating the effect of in-person school on SARS-CoV-2 cases and deaths per 100,000 persons during the 12-weeks following school opening, stratified by US Census region. There was no impact of in-person school opening and COVID-19 deaths. In most regions, COVID-19 incidence rates were not statistically different in counties with in-person versus remote school modes. However, in the South, there was a significant and sustained increase in cases per week among counties that opened for in-person learning versus remote learning, with weekly effects ranging from 7.8 (95% CI: 1.2–14.5) to 18.9 (95% CI: 7.9–29.9) additional cases per 100,000, driven by increases among 0–9 year olds and adults.