Abstract: This study was designed to compare between the efficacy of a phytobiotic containing a mixture of essential oils of Oreganum aetheroleum and an antibiotic containing ciprofloxacin as an active principle for the treatment of experimental (E. coli) infection in broiler chickens. Two hundred, day old broiler chickens were divided into 5 equal groups. The 1st group was neither challenged nor treated but groups 2, 3, 4 and 5 were challenged with E. coli. The 2nd group was challenged only while the 3rd, 4th and 5th group were treated with phytobiotic, ciprofloxacin and phytobiotic and ciprofloxacin combination, respectively. Results confirmed significant (p<0.05) improvement of productive performance parameters, reduction in signs, mortalities, post mortem lesions and bacterial re-isolation, significant (p<0.05) enhancement in cell mediated and humoral immune responses, significant (p<0.05) reduction in levels of liver and kidney function tests as well as significant (p<0.05) increase in the total protein and globulin levels in chickens challenged with E. coli and treated with either essential oils or ciprofloxacin compared with challenged non treated chickens. Moreover, the best significant (p<0.05) results in all measured parameters were detected in group treated with combination in comparison with those treated with single treatment. In conclusion, a mixture of essential oils of Oreganum aetheroleum is effective for the treatment of E. coli infection in broiler chickens when compared with ciprofloxacin. However, combined treatment could be superior in controlling such infection of broiler chickens.