BACKGROUND: While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there during the first epidemic wave in the first half of 2020. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 among individuals who visited 4 medical laboratories or 5 health centers for routine screening or clinical management, with the exception of symptomatic suggestive cases of covid-19. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. CONCLUSIONS/SIGNIFICANCE: The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p = 0.19) or age (p = 0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by French Guiana's young population structure.