Salmonellosis due to Salmonella enterica serovar Abortusovis (S. Abortusovis) is mainly characterized by abortion in sheep. Little is known about the immune response, which develops in the host as a result of infection. We evaluated the immune response of pregnant ewes vaccinated and successively exposed to full virulent S. Abortusovis. We found that vaccine constituted by inactivated S. Abortusovis induced both humoral and cellular-mediated immune response and that it provided protection against a challenge infection due to a fully virulent S. Abortusovis. Furthermore, we found an association between the lack of capability to produce IFN-gamma and abortion. This evidence suggests that protection against abortion can be associated to an IFN-gamma mediated mechanism. Our findings represent an interesting insight to better understand the interplay between host and S. Abortusovis and the effector mechanisms underpinning immune-based protection.