The study was goaled to compare the usage of probiotic and/or Fosfomycin in control of E. coli O78 in broiler chicken and the possible impact of these treatments on birds' immune reaction to ND vaccines. Two hundred and twenty birds were allocated to 11 with 20 birds per group and each group include two replicates with 10 birds each, the groups were as follows; G1 control negative birds; from G3 to G6 birds were challenged with strain 1(antibiotic resistant) E. coli O78 and G3, G4, G5 and G6 treated with Fosfomycin, Fosfomycin + probiotic, prebiotic and probiotic, respectively while G2 kept as control positive untreated birds. Birds from G7 to G11 were infected with strain 2 (antibiotic sensitive) E. coli O78 and G8, G9, G10 and G11 treated with Fosfomycin, Fosfomycin + probiotic, prebiotic and probiotic, respectively while G7 kept as control positive untreated birds. The results concluded that Fosfomycin may be a valuable tool in the management of antibiotic-resistant E. coli infections in broiler production in addition, the incorporation of probiotic supplementation may enhance the efficacy of Fosfomycin-based treatment by supporting intestinal health and the host's natural defense mechanisms.