The possible role of the most abundant structural protein of Rift Valley fever virus (RVFV), the nucleocapsid protein (NP), in inducing protective immune responses has only been evaluated preliminarily in mice but not in any natural host species. In this study we demonstrate that a soluble recombinant RVFV subunit NP in combination with adjuvants (ISA50, Alhydrogel, TiterMax Gold or SaponinQ) is highly immunogenic in mice and sheep but the level of clinical protection and virus replication in mice after lethal challenge was dependent on the adjuvant used. Immunization with NP in combination with Alhydrogel conferred 100% protection against morbidity, mortality and viral replication in mice, but sterilizing immunity could not be achieved in sheep with any NP/adjuvant combinations used. Although this is the first study showing that sterilizing immunity can be elicited in mice immunized with a RVFV subunit nucleocapsid protein, our findings seem to suggest that mice might not be the best animal model for studying the protective ability of RVF subunit vaccines. The results of our study also emphasize the importance of adjuvant selection when evaluating subunit RVF vaccines.