BEF is an immune related acute febrile disease affecting cattle characterized by expression of inflammatory mediators. This study aimed to clarify immune and inflammatory changes that result from BEF infection in cattle particularly cytokines mechanisms. The study was performed on 100 cattle, 2 - 3 years of age, from endemic areas with three-day sickness in Qaliubiya governorate, Egypt. Characteristic clinical signs appeared on cattle from suspected farms varied from transient fluctuating fever, stiffness, lameness, enlargement of peripheral lymph nodes, decreased milk yield and muscular shivering. So, we performed RT-PCR to confirm the cause of disease by direct detection of the virus targeting glycoprotein coding (G) gene , we found 30 cases positive BEF out of 100 animals. A negative control group was 10 healthy cows that was compared with positive infected group to show effect of virus on immune system by evaluating parameters change by infection, included endogenous pyrogenic variables such as cytokines, Interleukins (IL-2 and IL-6) and inflammatory biomarkers as (cortisone, CRP). Our results demonstrated substantial increase (P<0.05) in serum concentrations of IL-2, IL-6, cortisone and CRP as well as hypocalcemia in infected animals.