The efficacies of fosfomycin, thiampheicol and Nigella sativa oil were compared against experimentally infected chickens with E.coli O₁₁₁. One hundred and twenty six 12-day old broiler chickens were divided into seven groups:1^st group was control non infected non medicated , 2^nd group was infected with E.coli and non medicated, the 3^rd group was infected with E.coli and treated with disodium fosfomycin (40mg/kg b.wt), the 4^th group was infected with E.coli and treated with thiamphenicol (30mg/kg b.wt), the 5^th group was infected with E.coli and orally administrated with Nigella sativa oil  (0.025 ml/bird), the 6^th group was infected with E.coli and treated with disodium fosfomycin (40mg/kg b.wt), in addition to orally administration with Nigella sativa oil (0.025 ml/bird) and the 7^th group was infected with E.coli and treated with thiamphenicol (30mg/kg b.wt) in addition to Nigella sativa oil (0.025 ml/bird). The performance, clinical signs, E. coli reisolation, antibacterial activity and the effect on immune response of chickens were compared. The treated groups showed fewer symptoms and gross lesions than those of infected group. The body weight and average daily gain were highly improved in the 6^th, 7^th and 5^th group respectively. The combination of Nigella sativa oil with fosfomycin and thiamphenicol increase their antibacterial activity. The specific antibody titers against the E.coli O₁₁₁ were significantly increased in the groups which received Nigella sativa oil. The results indicate that addition of Nigella sativa oil with fosfomycin or thiamphenicol increases their efficacy, antibacterial activity and immune response against E. coli O₁₁₁.