Abstract Slovakia conducted multiple rounds of population-wide rapid antigen testing for SARS-CoV-2 in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% CI: 57-58%) within one week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1-6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared to a scenario of unmitigated growth was 70% (67-73%). Modelling suggests that this decrease cannot be explained solely by infection control measures, but requires the additional impact of isolation as well as quarantine of household members of those testing positive.