Climate change is influencing polar bear (Ursus maritimus) habitat, diet, and behavior but the effects of these changes on their physiology is not well understood. Blood-based biomarkers are used to assess the physiologic health of individuals but their usefulness for evaluating population health, especially as it relates to changing environmental conditions, has rarely been explored. We describe links between environmental conditions and physiologic functions of southern Beaufort Sea polar bears using data from blood samples collected from 1984 to 2018, a period marked by extensive environmental change. We evaluated associations between 13 physiologic biomarkers and circumpolar (Arctic oscillation index) and regional (wind patterns and ice-free days) environmental metrics and seasonal and demographic co-variates (age, sex, season, and year) known to affect polar bear ecology. We observed signs of dysregulation of water balance in polar bears following years with a lower annual Arctic oscillation index. In addition, liver enzyme values increased over time, which is suggestive of potential hepatocyte damage as the Arctic has warmed. Biomarkers of immune function increased with regional-scale wind patterns and the number of ice-free days over the Beaufort Sea continental shelf and were lower in years with a lower winter Arctic oscillation index, suggesting an increased allocation of energetic resources for immune processes under these conditions. We propose that the variation in polar bear immune and metabolic function is likely indicative of physiologic plasticity, a response that allows polar bears to remain in homeostasis even as they experience changes in nutrition and habitat in response to changing environments.