INTRODUCTION: In response to coronavirus disease 2019 (COVID-19), travelers are typically subject to quarantine, which is often associated with poorer mental health (MH). While the protective benefits of community-based exercise are widely recognized, the degree to which this extends to the confined setting is unknown. This systematic review aims to evaluate the effect of exercise on MH in isolating or quarantining adults. METHODS: A literature search of Ovid MEDLINE, APA PsycInfo, and the Cochrane Database of Systematic Reviews limited to January 2019-September 2021 inclusive yielded five eligible studies. RESULTS: Data comprised a total of 2755 college and university students, most of whom were confined. Depending on the scale used, 24.9-76.7% of respondents demonstrated impaired MH, which improved with physical activity (PA), especially when regular and moderate or vigorous. The frequency, duration, and participants of exercise increased as lockdown progressed. One study showed that while sleep, diet, and PA all have an impact on MH, PA was the factor most strongly correlated with MH. DISCUSSION: Physical fitness should be optimized before and maintained during quarantine while exercise space and equipment should be accessible. Importantly, the sustainability of persistent quarantine must be considered given the pervasiveness of COVID-19. Chu V, Newman DG. Exercise effect on mental health in isolating or quarantining adults . Aerosp Med Hum Perform. 2023; 94(9):686-695.