Ornithobacterium rhinotracheale is a Gram-negative bacterium associated with respiratory diseases in many avian species and it causes variable economic losses to the poultry industry. In this study, single aerosol infection of broiler chickens with three PCR confirmed local isolates of Ornithobacterium rhinotracheale (ORT) from Sharkia Governorate was found to cause growth retardation together with mild respiratory manifestations and 5-10% mortalities. Mild tracheitis, airsacculitis and pneumonia were observed post aerosol administration. Co-infection with E. coli was found to have triggered effect on ORT infection in broiler and cause a higher degree of pathogenicity, higher mortalities and severe growth retardation than the single infection. The three different isolates were found to cause nearly the same degree of inflammatory response. ORT infection alone resulted in minimal microscopic lesions in the trachea and air sacs.Mixed infection (ORT with E. coli) resulted in more severe lesions than those by ORT alone as well as dense lymphocytic infiltrations in tracheas, lungs, air sacs and hearts were shown. Amoxicillin was successfully improving the clinical signs and body weight gain of ORT infected birds.