Vaccination is a promising approach to prevent Klebsiella infection; however, the high heterogeneity of strains is a limiting factor. The best antigenic target for an anti-Klebsiella vaccine should be expressed by all or most of strains. We previously found YidR protein to be highly conserved among K. pneumoniae strains independently of antigen serotype. Therefore, in the present study, we developed a recombinant YidR protein vaccine and evaluated its protective efficacy against lethal challenge with K. pneumoniae in a mouse model. The yidR gene was cloned in Escherichia coli for recombinant expression. The lethal dose (LD) of K. pneumoniae was determined and lethal challenge was carried out after immunization with recombinant purified YidR. After immunization, the concentration of total serum IgG was significantly higher in YidR-immunized mice than in non-immunized mice, indicating strong induction of antibodies. Mice were challenged with LD of K. pneumoniae, and significantly lower murine sepsis and higher body weight were observed in YidR-immunized mice compared to unvaccinated controls. Moreover, ∼90% of YidR-immunized mice survived beyond 10 days of observation, whereas none of the control mice survived past 48 h. The protective effect of YidR recombinant protein vaccine was demonstrated and YidR may be a promising vaccine candidate to prevent klebsiellosis.