Rectal swabs and blood samples were collected from (100) diarrheic calves and (20) apparently healthy contact calves using sterile cotton swabs, at different farms in Sharkia Governorate. For hematological and biochemical investigations, a total of 20 blood samples with and without EDTA from healthy animals showed negative bacterial isolation (group 1) and 50blood samples were selected from collected blood samples (100) from animals showed positive bacterial isolation (group 2). Bacteriological examination of fecal samples revealed that E coli was the most prominent cause of calf  diarrhea at an incidence of 54.1 %,followed by Salmonella species at an incidence of  17.5 % then Campylobacter at an incidence of 10.8 %. Proteus valgaris was isolated at an incidence of 10 % then Pseudomonas at an incidence of 6.7 %. Serological identification of 65 E. coli isolates, revealed that the E. coli were typed as O157 (38.5%), O119 (23.1%), O25 (7.7), O111 (7.7%), O186 (15.4%), and untypable E. coli (7.7%). Bacteriological examination revealed the isolation of Salmonella from diarrheic calves as well as apparently healthy contact calves. S. typhimurium was the most predominant serovars (52.4%) which indicates that S. typhimurium is the most predominant serovars causing enteritis in calves. S. enteritidis (33.3%) and 3 strains (14.3%) were untypable. Results of antibiogram revealed that, ciprofloxacin, cephalexin and ofloxacin( were the most effective antibiotics for treatment of diarrheic calves. Most isolated bacteria showed different degrees of resistance to Ampicillin, Cefotaxime, Gentamycine. PCR results revealed that 16 (88.9%) out of 18 examined E coli strains encoding blaTEM gene while only two (11.1%) strains were negative. The hematological changes revealed  that  there was a significant decrease in total red blood cells count, platelets and hemoglobin concentration (p < 0.05) accompanied by higher values  of Total leukocyte count (TLC), neutrophilia with lymphopenia recorded in diarrheic calves in comparison with control.Biochemical analysis  of  positive  cases revealed  significant increase (P<0.05)  in serum globulin content and decrease in  total protein, albumin content, resulting  in altered A/G ratio, also there was significant increase in urea, creatinine and potassium  accompanied  by significant decrease in glucose and sodium. In comparison with control amino acid analysis demonstrated significant (P<0.05) decrease in diseased calves. Inter nucleosomal cleavage of host cell DNA, indicated evidence of apoptosis, there was a direct relationship between DNA fragmentation and malondialdehyde level (MDA) while inverse relation with antioxidants.