Selenium plays a role in the antioxidant mechanism via the selenoenzyme glutathione peroxidase (GSH-Px). Change in Se status because of Se depletion or supplementation is associated with a change in GSH-Px activity and could potentially affect antioxidant status. This study evaluated the impact of change in Se status on measures of antioxidant status and oxidative stress in adult horses. Twenty-eight horses were blocked by age and gender and were randomly allocated to 1 of 4 dietary treatment groups: low Se (LS), adequate Se (AS), high organic Se (SP), and high inorganic Se (SS). For 196 d, LS, SP, and SS received a low-Se diet (0.06 mg Se/kg DM) to allow for depletion of Se stores, whereas AS received an adequate Se diet (0.12 mg Se/kg DM). Then, for the next 189 d, LS and AS were maintained on the same diets, whereas SP was supplemented with Se-yeast and SS with sodium selenite to allow for a total dietary Se intake of 0.3 mg Se/kg DM. Blood samples were collected throughout the study. Variables of interest included whole blood Se and GSH-Px activity, serum vitamin E concentration, total antioxidant capacity (TAC), serum malondialdehyde (MDA), and triiodothyronine and thyroxine concentrations. Data were analyzed using ANOVA with repeated measures. Whole blood Se and GSH-Px activity decreased in LS, SP, and SS during the depletion phase and increased in SP and SS with supplementation (treatment × time, P < 0.001). At the conclusion of the supplementation period, GSH-Px activity was greater in SP and SS compared with AS and LS (P < 0.05). Vitamin E status remained adequate throughout the study, and no differences existed between treatments. Serum TAC did not change in response to Se depletion or repletion. Serum MDA was greater for AS than LS during depletion (P < 0.05) but similar across treatments after supplementation. Overall, change in Se status did not have a large impact on TAC or MDA, possibly because the horses maintained an adequate vitamin E status. However, Se supplementation at 0.3 mg/kg DM increased GSH-Px activity above that of the horses fed an adequate diet based on the 2007 NRC recommendations, indicating a potential benefit to feeding greater Se diets to horses kept in low-Se areas.