BackgroundNonpharmaceutical interventions, including face mask-wearing, physical distancing, and avoidance of crowds and poorly ventilated spaces, have been widely recommended to limit the spread of SARS-CoV-2. To date, there is little data available on engagement in nonpharmaceutical interventions and COVID-19 in college students. Using a large sample of college students, we estimate the prevalence of engagement in mask-wearing, physical distancing, and avoidance of crowds/poorly ventilated spaces and their associations with COVID-19.MethodsA cross-sectional study was conducted (February–March 2021) using a college-wide online survey among students (n= 2,132) in California. Multiple modified poisson regression models assessed associations between mask-wearing indoors, physical distancing (both indoors or public settings/outdoors), avoidance of crowds/poorly ventilated spaces and COVID-19, controlling for potential confounders.ResultsFourteen percent (14.4%) reported a previous COVID-19 illness. Most students reported wearing masks consistently indoors (58%), and 78% avoided crowds/poorly ventilated spaces. About half (50%) reported consistent physical distancing in public settings/outdoor and 45% indoors. Wearing a mask indoors was associated with 26% lower risk of COVID-19 disease (RR = 0.74; 95% CI: 0.60,0.92). Physical distancing indoors and in public settings/outdoors was associated with a 30% (RR = 0.70; 95% CI: 0.56,0.88) and 28% (RR = 0.72; 95% CI: 0.58,0.90) decrease risk of COVID-19, respectively. No association was observed with avoidance of crowds/poorly ventilated spaces. The risk of COVID-19 declined as the number of preventive behaviors a student engaged in increased. Compared to those who did not engage in any preventive behaviors (consistently), students who consistently engaged in one behavior had a 25% lower risk (RR = 0.75; 95% CI: 0.53,1.06), those who engaged in two behaviors had 26% lower risk (RR = 0.74; 95% CI: 0.53,1.03), those who engaged in three behaviors had 51% lower risk (RR = 0.49; 95% CI: 0.33,0.74), and those who consistently engaged in all four behaviors had 45% lower risk of COVID-19 (RR = 0.55; 95% CI: 0.40,0.78).ConclusionsWearing face masks and physical distancing were both associated with a lower risk of COVID-19. Students who engaged in more nonpharmaceutical interventions were less likely to report COVID-19. Our findings support guidelines promoting mask-wearing and physical distancing to limit the spread of COVID-19 on campuses and the surrounding communities.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-023-15916-0.