<p>The present study was conducted to compare the effect of Nano-Selenium (Nano-Se) and sodium selenite (SSe) on antioxidant enzyme activity, immunity and thyroid activity of growing New Zealand White (NZW) rabbits. In this study, 72 male rabbits (5 wk old) were divided randomly into 3 groups (24 rabbits each). The first group served as a placebo; in groups 2 and 3, each rabbit was intramuscularly injected once a week with 4 mL solution of Nano-Se or SSe, respectively, for a 2-mo period. The solution was adjusted to provide 30 μg Se/kg/live body weight. Results showed that Nano-Se treatment significantly (<em>P</em><0.0001) increased in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) more than control, but decreased significantly each of glutathione disulphide (GSSG) and nitric oxide (NO) levels in serum. Likewise, supplementation of SSe increased (<em>P</em><0.0001) GPx activity and significantly decreased both malondialdehyde (MDA) and GSSG levels more than control. Nano-Se significantly enhanced serum IgG and IgM more than SSe and control groups. Serum aspartate aminotransferase increased (<em>P</em><0.0001) due to Nano-Se treatment as compared to control and SSe, although the lowest (<em>P</em><0.0001) activity of alanine aminotransferase was recorded due to SSe supplementation. Nano-Se treatment increased (<em>P</em><0.0001) both T3 and T4 concentrations more than other groups. Furthermore, administration of Nano-Se increased SOD, GPx, GSH, total antioxidant capacity (TAC) and adenosine triphosphate (ATP) in liver tissue of growing rabbits, while it decreased MDA and 8-hydroxy-2’deoxyguanosine (8-oHdG) levels in liver tissue compared with control. Also, SSe showed an increase (<em>P</em><0.0001) in GSH, and ATP, but significantly decreased TAC and MDA levels compared with control. It can be concluded that Nano-Se supplementation significantly enhanced the activity of antioxidant enzymes in both serum and liver tissues, with a greater positive influence on immunoglobulin production and thyroid activity in growing NZW rabbits than SSe.</p>