BACKGROUND: Facemasks are used to minimize SARS-CoV-2 spread during the COVID-19 pandemic. However, facemask use during exercise is associated with possible adverse effects. OBJECTIVES: To compare the effects of facemask use vs. non-facemask use on subjective responses, COVID- 19 incidence, and physiologic changes in healthy adults during exercise. METHODS: The systematic review (PROSPERO registration number: CRD42022296247) will follow the PRISMA-P guidelines and use electronic databases Science Direct, PubMed, Google Scholar, Herdin, and EbscoHost. This will cover randomized parallel groups or randomized crossover studies investigating tolerability, physiologic effects, and the impact on SARS-COV2 incidence of commercially-available cloth, surgical, or FFR/N95 facemasks compared to no-facemask conditions during exercise among healthy adults, including studies published from the earliest date to January 31, 2022. Outcomes of interest will be facemask tolerability in 10 domains of comfort and objective cardiopulmonary, gas exchange, and metabolic responses. Mean differences (MD) or standardized mean differences (SMD) with a 95% confidence interval (CI) will be calculated overall and for subgroups using RevMan software (version 5.4.1). Pooled and subgroup estimates will be calculated using random-effects meta-analysis. The chi-squared test, I2 statistics, and visual analysis will assess heterogeneity. The GRADEpro will determine the certainty of the level of evidence. EXPECTED RESULTS An evidence-based recommendation using GRADE on the changes attributed to facemask use during exercise will be available. This will be useful for organizations when developing appropriate guidelines for exercising while mitigating the risk of SARS-CoV-2 transmission. Future researchers may use this study when redesigning comfortable facemasks without compromising filtration capability.