Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food animals of the Arctic, and arctic indigenous peoples may be exposed via consumption of subsistence-harvested animals. PFASs are suspected of disrupting thyroid hormone homeostasis in humans. The aim of this study is to assess the relationship between serum PFASs and thyroid function in a remote population of Alaska Natives. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and total thyroxine (T4), free and total triiodothyronine (T3), and thyrotropin (TSH) were quantified in serum samples. The relationships between circulating concentrations of PFASs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T3 and PFNA was significantly associated with total T3 in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T4. Serum PFASs are associated with circulating thyroid hormone concentrations in a remote population of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis may differ between sexes.