BackgroundWastewater-based surveillance is a valuable tool for monitoring pathogen transmission in communities, especially in regions where formal surveillance systems are limited. AimThe aim of this study was to implement and evaluate a wastewater-based monitoring system for viral pathogens in São Tomé and Príncipe. MethodsA total of 122 water samples were collected bi-weekly from June 2022 to July 2023 at six locations in São Tomé city and analysed for molecular detection of Hepatitis A Virus (HAV), Enterovirus (EV), Poliovirus (PV), SARS-CoV-2, as well as JC-Polyomavirus (JCPyV) and pepper mild mottle virus (PMMoV) as indicators of human contamination. Prevalence was analysed per pathogen and across sampling locations. Results for SARS-CoV-2 were assessed together with notifications from national COVID-19 surveillance. Further, we estimated resources needed to establish a wastewater-based approach to assess community-level transmission of viral pathogens. ResultsAll 122 and 117 samples were found positive for PMMoV and JCPyV, respectively, demonstrating a high level of human contamination at all sampling locations. The prevalence of HAV and EV ranged from 0 % to 59 % and 56 % respectively. Consistent with national surveillance data the highest proportion of SARS-CoV-2 positive water samples coincides with the highest number of COVID-19 cases reported during the study, demonstrating the potential of wastewater-based surveillance to identify signals. In addition, for SARS-CoV-2 this approach provided evidence of continuous circulation of the virus in the community, most importantly during weeks when no COVID-19 cases were reported. ConclusionOur findings provide evidence of high transmission of HAV and EV in communities in São Tomé and continuous circulation of SARS-CoV-2, even in weeks without COVID-19 case notifications. This study demonstrates that monitoring of viral pathogens in humanly impacted open water streams and sewage tanks is a valuable tool to complement clinical surveillance in resource-limited settings.