Background: Many Arctic Indigenous communities are disproportionately exposed to persistent bioaccumulative toxicants due to global distillation and traditional diets. There is relatively little known about sources of exposure to PFAS in Arctic Indigenous Communities. Aim: The aim of this study was to assess exposure to, and health effects of, PFAS in two Arctic Indigenous communities on Sivuqaq (St. Lawrence Island), Alaska. Methods: Working within an established community-based participatory research program we assessed exposure to PFAS using human serum samples, indoor dust, traditional foods, as well as sentinel fish species. Results: Community members on Sivuqaq have broadly similar PFAS exposures to the U.S. population as measured by NHANES; however, select long chain PFAS such as PFNA and PFUNA appear elevated among Sivuqaq residents. Several PFAS are associated with circulating thyroid hormone concentrations in this this population. PFAS are present in traditional food animals as well as sentinel fish species collected in Sivuqaq. Sentinel fish suggest some aspect of the built environment acts as a point source of PFAS. Fish data also suggest strong species level effects in accumulation of PFAS. Dust concentrations of PFAS are on the low end of those reported and suggest the indoor environment may be a comparatively minor contributor to serum PFAS in this population. Discussion: Alaska Native communities are exposed to PFAS through multiple routes of exposure. This may result in elevated exposure for select PFAS. Serum PFAS are associated with measures of thyroid function.