Objective: In view of the current COVID-19 pandemic, the objective of this study was to determine, through a systematic review and meta-analysis, whether the use of N95/FFP2 masks during aerobic exercise has a significant impact on HR, RR, SpO2, and blood pressure (BP) in healthy individuals. Methods: We searched the MEDLINE database for studies published in English between 2005 and 2021. To reduce bias and increase reliability, only randomized controlled trials and randomized crossover clinical trials were considered for inclusion. The selected outcomes included HR, RR, SpO2, and BP, with perceived exertion being evaluated by means of the Borg scale. Results: Eight controlled trials were included in the meta-analysis. Seven evaluated HR (p > 0.05), five evaluated RR (p > 0.05), five evaluated SpO2 and BP (p > 0.05 for both), and six evaluated perceived exertion, presenting controversial results such as risk ratios that were grouped for each variable. Conclusions: This study suggests that N95 and FFP2 masks do not have significant effects on HR, RR, SpO2, and BP during aerobic exercise in healthy individuals.