The effect of bovine viral diarrhea virus (BVDV) infection and Aflatoxine BI (AFBI) on the immune response of sheep vaccinated with bivalent Foot and mouth disease (FMD) vaccine were studied. Significant decrease in humoral immune response against the vaccine strains 01/3/93 and A/l/Egypt/2006 accompanied by protection percentage of 33% against challenged virus 01/3/93 with low values of AOD were recorded in sheep previously infected with BVDV one week before vaccination. Challenging the immunity of sheep both simultaneously infected with BVDV and vaccinated or infected one week post vaccination against 01/3/93 revealed protection percentages of 66%. Sheep fed on commercial ration treated with 40gykgm ration of prepared AFB and challenged at three weeks post vaccination showed protection percentage of 33%, decrease in antibody titers and low values of AOD. The immunosuppressive effects of BVDV and AFBI on the immune response of sheep vaccinated with bivalent FMD vaccine were discussed.