Over six month period from July to December 2013, investigation of poor performance problem was carried out among meat type chicken populations that routinely immunized against Newcastle, Infectious bursitis, Infectious bronchitis and Avian Influenza at Minia El-kameh, Sharkia governorate, Egypt. Seventy stunted birds of different breeds aged between 20 and 40 days old were selected from eight private farms. Post mortem examination incriminated probable infection of Reo virus and E. coli. Total of 350 organs (provintireculus, pancreas, small intestine, thymus and heart) sampled for REO and 420 (liver, spleen, lung, joint, bile, heart blood) for E. coli isolation. Results showed that 35 (10%) were positive REO virus identified by agar gel precipitation test and 34 (8.1%) E coli serotyped O₅₅, O₇₈, O₁₁₉ and O₁₂₅. One hundred and forty day old chicks were deployed to conduct two experimental infections of the isolated virus and bacteria via different routes to evaluate its effect on chicken's performance and histological changes. In each experiment chickens were divided into 3 groups, 1 and 2 were infected with E. coli O₇₈ or REO while third group remained uninfected, served as control. Intramuscular infected groupsrecorded the highest mortalities and lower body weight comparing with oral and ocular route. Reisolation and histopathological changes confirmed pathogenicity of E. coli O   and REO virus respectively. It is recommended that further studies to be done on REO diversity and molecular characterization in Egypt whilst adoption of vaccination programs against Reo virus and E. coli infection especially for breeder hens considered an utmost need to avoid serious economic losses.