Island rodents are often larger and live at higher population densities than their mainland counterparts, characteristics that have been referred to as “island syndrome”. Island syndrome has been well studied, but few studies have tested for island-mainland differences in stress physiology. We evaluated island syndrome within the context of stress physiology of white-footed mice ( Peromyscus leucopus ) captured from 11 islands and five mainland sites in Thousand Islands National Park, Ontario, Canada. Stress physiology was evaluated by quantifying corticosterone (a stress biomarker), the primary glucocorticoid in mice, from hair and its related metabolites from fecal samples. White-footed mice captured in this near-shore archipelago did not display characteristics of island syndrome, nor differences in levels of hair corticosterone or fecal corticosterone metabolites compared with mainland mice. We suggest that island white-footed mice experience similar degrees of stress in the Thousand Islands compared with the mainland. Although we did not find evidence of island syndrome or differences in glucocorticoid levels, we identified relationships between internal (sex, body mass) and external (season) factors and our hormonal indices of stress in white-footed mice.