PROJECT SUMMARY Wastewater-based epidemiology (WBE) is a powerful tool that can measure population health in communities with centralized sewer treatment systems and is particularly relevant for Tribes who wish to assess health disparities such as COVID and substance abuse. In WBE, chemical metabolites, bacteria and viruses, and other health indicators are measured in excreted human waste products in wastewater. The wastewater flow rate and population load into the sewershed allow for calculation of community-level human health indicators present in water. WBE has not been documented in Tribal communities prior to the PI’s efforts, and there are knowledge gaps related to the execution, acceptability, and applicability of this tool to assess Tribal population health. Our specific aims are to (1) develop a framework for conducting responsible WBE research and surveillance in Tribal communities, which will address data sovereignty, Tribal sewer infrastructure and personnel, and handling of environmental biospecimens; (2) assess the perceptions of using WBE by Tribal leaders, health administrators, and community members through surveys; and (3) determine and quantify relevant health metrics that can be measured by WBE, including infectious disease, pollutant exposure, the gut microbiome, and substance abuse. This faculty enhancement award under ITCA’s NARCH XI will provide directed mentorship and training to the PI from ITCA staff. This collaborative project will develop research capacity for ITCA, partner Tribes in Arizona and the faculty member through collection of preliminary data, leading to development of larger projects with ITCA and the partner intertribal consortia for future WBE studies.