Trace element selenium occupies a privileged position among the natural antioxidant in addition to its ability to enhance the immune response in several species. The current challenges of supplementation of sodium selenite in poultry diets are always linked to low absorption and increased toxicity. Therefore, it is imperative to embrace new technologies like nanotechnology to get as an alternative source of traditional selenium supplementation in form of the nanoparticles with high bioavailability and low toxicity which will be positively reflected on biological activities of selenium. The present study was conducted to investigate the antioxidant and immunomodulatory effects of different concentrations of Nano-selenium on response of broilers to ND vaccination. A total of one hundred and eighty day old Cobb broilers were randomly allocated in 6 groups with each group applied to 3 replicate of 10 chicks, the first two groups were control negative groups without selenium supplementation and the remaining four groups were dietary supplemented with sodium selenite (0.15ppm) and Nano-selenium at concentration of  (0.15ppm), (0.075 ppm) and (0.0375 ppm), respectively. The results showed that Nano-selenium had a superior effect compared to that of the sodium selenite either as an antioxidant or as an immunomodulatory and comparing the control negative groups. The most important results can be summarized in the following points; significant improvement in Feed conversion ratio (FCR), significant enhancement in activities of antioxidant enzymes without adverse effects on tested biochemical parameters as well as significant boosting in antibody titers against ND. In conclusion, Nano-selenium supplementation in commercial broilers diets could be an economically a promising multitask option, particularly when it comes to improving antioxidative status and boosting immune response to NDV (LaSota) vaccination  in broilers.