Mercury (Hg) is a widespread contaminant that has been shown to induce adverse health effects in a wide range of organisms. We explored the relationship between total blood Hg concentrations ([Hg]) and oxidative stress induction in double-crested cormorants (Phalacrocorax auritus). Cormorant blood was sampled at five sites across the Great Lakes basin, Ontario, Canada and was analyzed for total [Hg].To assess cellular stress, the expression of glutathione peroxidases 1 and 3, glutathione S- transferase µ3, superoxide dismutase 1 and heat-shock protein 70 kd-8 were measured in whole blood samples. No significant variations in mean relative gene expression were found between sites for any gene for all birds. Linear regression analyses showed a slight, significantly positive relationship between individual blood [Hg] and gpx3 expression for all birds. However, when separated by sex, there were differences. Male cormorants displayed higher blood Hg concentrations than females. Female individuals showed significant positive relationships between blood Hg concentration and expression of glutathione peroxidase 3 and glutathione S-transferase μ3. Different levels of oxidative stress experienced by males and females during the breeding season may be influencing the differential oxidative stress responses to blood [Hg] observed in this study. Overall, the results of our study suggest that Hg leads to oxidative stress in the blood of P. auritus and that this oxidative stress is mediated by upregulation of gstm3 and gpx3 expression.