The extraction of bitumen in areas of northeastern Alberta (Canada) has been associated with the release of complex mixtures of metals, metalloids, and polycyclic aromatic compounds (PACs) to the environment. To mitigate effects on ecosystems, Canadian legislation mandates that disturbed areas be reclaimed to an ecologically sustainable state after active operations. However, as part of reclamation activities, exposure to, and effects on wildlife living in these areas is not generally assessed. To support successful reclamation, the development of efficient methods to assess exposure and health effects in potentially exposed wildlife is required. In the present study, we investigated the usefulness of two native mammalian species (deer mouse Peromyscus maniculatus, and meadow vole Microtus pennsylvanicus) as sentinels of oil sands related contaminants by examining biomarkers of exposure and indicators of biological costs. Tissue residues of 31 metals and metalloids in kidneys and muscle, activity of the hepatic detoxification enzyme EROD (as a biomarker of exposure to organic contaminants), body condition, and the relative mass of liver, kidney, spleen, and testes were compared in animals from one reclaimed area and a reference site. Deer mice from the reclaimed site had higher renal levels of Co, Se and Tl compared to animals from the reference site, which was associated with reduced body condition. Lower testis mass was another feature that distinguished mice from the reclaimed site in comparison to those from the reference site. One mouse and one vole from the reclaimed site also showed increased hepatic EROD activity. In marked contrast, no changes were evident for these variables in meadow voles. Our results show that deer mouse is a sensitive sentinel species and that the biomarkers and indicators used here are efficient means to detect local contamination and associated biological effects in native mammals inhabiting reclaimed areas on active oil sands mine sites. These field-derived findings can be used by risk assessors to fill possible data gaps for mammalian wildlife in science-based environmental risk assessments for oil and gas projects.