The aim of this study was to highlight the importance of using PCR to investigate the most important and common pathogens causing calf diarrhea. In addition, to characterize the profiles of some inflammatory cytokines, acute phase proteins, oxidant-antioxidant status, and some immune parameters to clarify their clinical importance during the course of the disease. The study was conducted on 44 calves, 31 calves were suffering from diarrhea manifestations based on clinical examination (diseased group). The rest 13 calves were apparently healthy and were served as control group. Blood samples were collected from both groups and were assayed for the selected biochemical and immunological parameters. Fecal samples collected directly from the rectum of diarrheic calves were subjected to PCR technique for detecting 5 major bovine enteric pathogens including bovine Coronavirus, bovine Rotavirus, Salmonella spp., E. coli, and Cryptosporidium parvum. The results of PCR indicated that E. coli, Salmonella and Cryptosporidium were the most important pathogens isolated from diarrhetic calves at percentages of 38.7 %, 25.8 % and 12.9 % respectively. On the other hand, Rota and Coronaviruseswere not demonstrated in diarrheic calves. Regarding the selected biochemical and immunological parameters, the results showed that compared to control group, the diseased calves demonstrated significant increases in IL-6, ceruloplasmin, haptoglobin, malondialdehyde and nitric oxide. Significant decreases were observed in total antioxidant capacity, IL-10 and IgA, while no significant changes were reported in serum levels of IgG and IgM. In conclusion, the presented results can document that E. coli, Salmonella and Cryptosporidium are among the most important pathogens resulting in calf diarrhea. The results also provide a confirmation about the importance of proinflammatory cytokines in signaling in the development of calf diarrhea probably through oxidative stress which may rise their values as therapeutic targets for treating diarrhea in calf.