This work was designed to investigate the effect of yeast( Saccharomyces cerevisiae) and Sangrovit as natural feed additives on chicken production performance, some hematological parameters, some biochemical parameters, histopathological examination of (liver and kidney) and total coliform count of intestinal content in normal and experimentally infected chickens with E.coli O78. A total of 120 unsexed one-day-old, broiler chickens (Cobb) were randomly assigned to 6 treatment groups each of 20 as follows: G1 as the control; G2 received 0.3% Yeast supplement; G3 received 0.1% Sangrovit supplement; G4 infected by E.coli only; G5 infected by E.coli and treated by 0.3% Yeast and G6 infected by E.coli and treated by 0.1% Sangrovit. Our work revealed that Yeast and Sangrovit as feed additives have marked impacts on growth-promoting, immunomodulating and antimicrobial effects with no adverse effects on haematological and serum biochemical parameters and can contribute in controlling and prevention of E.coli induced experimental infection in broiler chicken.