This study was carried out to determine the immunomodulating effect of β-glucans and mannan oligosaccharide (MOS) on the immune response of chickens to Newcastle disease vaccine. The results showed that birds received β-glucans and MOS having higher average body weights values and significantly higher ND HI antibody titer than the other non medicated groups. Thymus, spleen and bursal indices of control negative showed significantly lower values than vaccinated medicated and non-medicated groups. Both total and differential leukocytic and lymphocytic counts showed significantly higher in medicated group than other groups. Liver function test showed lower AST and ALT in medicated group than other groups. Results of challenge test with NDV confirmed that MOS and B glucans immunostimulant improved protection rate by 15% in medicated than non- medicated ones. In conclusion MOS and B glucans can be given to chicken to improve both body weight and protection against VV NDV challenge that predominated in Egypt.