An experiment was conducted to determine the differences in the humoral and cell mediated immune responses of cattle to tissue culture adapted-lumpy skin disease (LSD) and sheep pox (SP) viral vaccines. Concerning humoral immune response, both viruses induced high antibody titres as measured by serum neutralization test and ELISA . No significant differences in the ability of sera of cattle vaccinated with SPV or LSDV vaccines to neutralize both viruses were detected. This indicated that epitopes responsible for humoral immune response are cross-reactive to a higher degree in both viruses. Concerning the cell-mediated immune response, peripheral blood lymphocytes from animals vaccinated with LSDV and stimulated with inactivated LSDV (homologous mitogen) showed higher stimulation percentage than those stimulated with inactivated SPV (heterologous mitogen), This indicated that LSDV as a vaccine produces better cell mediated immune response specific against LSDV which has a significant role in protection of animals against virulent field LSDV infection.