This study was carried out to illustrate the effects of Bacillus subtilis probiotic (Baymix®) and chelated zinc (Availa zinc®) in prevention of E. coli in poultry farms and also to examine their effects on some blood biochemical, immunological parameters and antioxidant status in broiler chickens. One hundred and fifty one day old cobb chicks were used in this study. The chicks were divided into six groups, each group contain 25 chick, the 1 st group was (control) non infected and fed balanced diet without additives, 2 nd group was non-infected treated with probiotic (NPRO), 3 rd group was non-infected treated with chelated zinc (NZn), 4 th group was infected non treated (INT), 5 th group was infected treated with probiotic (IPRO) and 6 th group was infected treated with chelated zinc (IZn). The infection by E.coli (078) occurred at 21 st day of age. Blood samples collected for biochemical parameters, phagocytic activity detection. Liver tissues collected for some antioxidant parameters (MDA and GPx), some immunological parameters interleukin-1β (IL-1β), interferon gamma (IFNγ) and interleukin-10 (IL-10), The results showed that were no significant changes in serum uric acid, creatinine, ALT and AST and significant decrease in malonaldehyde (MDA) and increases in glutathione peroxidase (GPx), phagocytic activity and immunological parameters (IL-1β, IFNγ, IL-10) in NPRO and NZn groups compared to control group and significant decreases in serum uric acid ,creatinine, ALT and AST and significant decrease in MDA and significant increase in glutathione peroxidase (GPx), phagocytic activity and immunological parameters IPRO and NZn groups compared to INT group. From this study we could conclude that the use of B. subtilis probiotic and chelated zinc improve kidney and liver functions, antioxidant status, phagocytic activity and immune response in broilers chickens infected with E. coli (078).