Salmonella enterica has long been recognised as an important zoonotic pathogen of economic significance, both in animals and humans. We have recently shown that inactivation of the ZnuABC high affinity zinc transporter significantly affects the pathogenicity of S. enterica, likely due to zinc shortage in the eukaryotic tissues. Here, we demonstrate that a S. enterica serovar Typhimurium znuABC deleted strain is able to induce a short lasting infection in mice. On the same time, it primes a cell-mediated immune response, which confers a solid and durable immune-based protection against challenge infections with virulent strains of S. Typhimurium. These findings suggest the possibility to explore the use of S. enterica ZnuABC deleted mutants for the production on novel vaccines.