ABSTRACTBACKGROUNDSocial distancing mandates (SDM) have reduced health impacts from COVID-19 but also resulted in economic downturns that have led many nations to relax SDM. Until deployment of an efficacious and equitable vaccine, intervention options to reduce COVID-19 mortality and minimize restrictive SDM are sought by society.METHODSA susceptible-exposed-infectious-recovered (SEIR) deterministic transmission model was parameterized with data on reported deaths, cases, and select covariates to predict infections and deaths from COVID-19 through March 01, 2021. We explore three scenarios: a “non-adaptive” scenario where neither mask use or SDM adapt to changing conditions, a “reference” where current national levels of mask use are maintained and SDM reintroduced when deaths rise, and an increase in mask use to 95% coverage levels (“universal mask”). We reviewed published studies to set priors on the magnitude of reduction in transmission through increasing mask use.RESULTSMask use was estimated at 59.0% of people globally on October 19, 2020. Universal mask use could avert 733,310 deaths (95% UI 385,981 to 1,107,759) between October 27, 2020 and March 01, 2021, the difference between the predicted 2.95 million deaths (95% UI 2.70 to 3.35) in the reference scenario and 2.22 million deaths (95% UI 2.00 to 2.45) in the universal mask scenario over this time period.CONCLUSIONSThe cumulative toll of the COVID-19 pandemic could be substantially reduced by the universal adoption of masks before the availability of a vaccine. This low-cost, low-barrier policy, whether customary or mandated, has enormous health benefits with presumed marginal economic costs.