Background and Objective: The negative effects of preservatives, such as sodium benzoate, have received increasing global attention. The objective of the study was to investigate the potential protective effects of nano-selenium (nano-Se) on thyroid functions, oxidative stress and inflammatory cytokine responses of albino rats. Materials and Methods: Thirty-five male rats were divided into five groups, 7 rats in each: GI: A control group, GII: Corn oil, GIII: Nano-selenium, GIV: Sodium benzoate, GV: Selenium nanoparticles followed with sodium benzoate. At the end of study, sera were separated from all rats for estimation of MDA, GSH, GSH-PX, glucose, interleukin-1ß, TSH, T3, FT3, T4 and FT4. All data were statistically analyzed using Analysis of Variance (ANOVA). Results: Sodium benzoate treatment showed opposite effects as it decreased levels of T3, FT3, F4, FT4, GSH and GSH-PX. On the contrary, it increased serum levels of TSH, MDA, NO, glucose and IL-1$ when compared to the control group. Whereas, nano-selenium promoted a significant increase in levels of thyroid hormones T3, T4 and FT4, upgrading GSH and GSH-PX. While it reduced TSH, MDA, NO, glucose and IL-1$ levels when compared to the sodium benzoate group. Conclusion: Nano-selenium treatment as a protector showed the ability to reduce lipid peroxidation and restore glutathione peroxidase activity, thus, selenium complex at nano-level can reduce oxidative stress and damage of thyroid hormones caused by sodium benzoate administration