ABSTRACT Background: French Guiana (FG) is an ultra-peripheral European region in the Amazon, and the COVID-19 epidemic has had very different kinetics from both its giant neighbors, Brazil or mainland France. Methods: This study summarized the epidemics of COVID-19 in FG. Results: The tropical climate, multiethnicity, and remoteness of the population forced healthcare providers to accordingly adapt the management of the epidemic. Incidence and mortality have been lower than that in Europe and Latin America due to a combination of prevalence of the youth in the population and highly developed healthcare system. Conclusions: Currently, vaccine hesitancy hinders the rapid expansion of vaccine coverage.