This study was carried out on 80 buffalo-calves aged from 1-3month from private farms in Sharkia Governorate. Diseased calves were suffering from severe dyspnea, cough, nasal discharge, pyrexia and abnormal lung sounds. These calves were admitted for necropsy, pulmonary lobes mainly cardiac, diaphragmatic showed focal pneumonia areas (firm dark to red areas) involve the majority of lungs lobes and focal cavitations with presence of milky substitute inside the respiratory passages. Bacteriological examination of 155 samples (20from clinically healthy, 35from clinically diseased and 100 samples from each the nose, trachea, lungs and regional lymph nodes of 25 freshly dead and emergency slaughtered calves) revealed that 140 (90.3%) samples from clinically healthy calves, diseased and freshly dead and emergency slaughtered calves were positive for bacterial infection where 103(73.6%) were as a single infection identified as E. coli 70 (68.0%), Staph. aureus 20 (19.4%) and Streptococcus pneumoniae 13 (12.6%), however 37 (26.4%) were mixed infection identified as E. coli with Staph. aureus 27 (73.0%) and Strept. pneumoniae 10 (27.0%). The results of the antimicrobial sensitivity test showed that Enrofloxacin, Ceftiofur, Erythromycin and Florofenicol were the most effective antibiotics for treatment. The histopathological findings revealed gangrenous , fibrinopurullent pneumona , focal areas of pneumona in the lung tissues with milk substitute mass inside the bronchioles. Perivascular edema with thickened inter alveolar septa beside emphysema in the adjacent pulmonary tissues were seen. Also liver showed hepatitis and necrosis of hepatocytes. It could be concluded that the using of milk substitute in calves feeding may be induce serious respiratory problems and deaths among suckling calves. ,