Sodium fluoride used in the fluoridation of drinking water and it is still commonly used for that purpose to prevent dental caries. It exerts toxic effects on many soft tissues. The present study was aimed to achieving the protective effects of selenium and Curcumin extract against the toxicity and oxidative stress of sodium fluoride (NaF) that adversely affects the immune system capacity. This study evaluated the effects of Sodium fluoride on some immunological parameters and also assessed the ameliorating effects of selenium and Curcumin extract. Mature male mice (weighing 35-45 g and each group of ten animals) were given sodium fluoride (10.3 mg/Kg bw) and/or Selenium (0.5 mg/Kg) + Curcumin extract (60 mg/Kg) daily intraperitoneally (I.P) for 4 weeks. In the present study, Sodium Fluoride exposure resulted in decrease in the IgG, IgM and increasing TNF-± level with respect to the control. As a result, Sodium fluoride induced immunotoxicity which is reduced by Curcumin extract and/or selenium to great extent by restoration of the immunological capacities.