Klebsiella pneumoniae remains a leading cause of neonatal sepsis in low-to-middle income countries. With the rapid emergence of multidrug resistant strains and the lack of novel antibiotics in the pipeline, there is an urgent need for alternative preventative strategies, such as vaccines, to combat K. pneumoniae infections. Several K. pneumoniae vaccines are in development, however, the lack of a reliable small animal model of K. pneumoniae-associated neonatal sepsis is a significant barrier for preclinical evaluation of vaccine efficacy. In this dissertation, we developed and characterized a K. pneumoniae neonatal sepsis mouse model. We demonstrated that 2- to 3-day-old C57BL/6 mice were highly susceptible to K. pneumoniae B5055, a serotype O1:K2 hypervirulent strain, following peroral infection. Additionally, neonatal mice exhibited an age- and dose-dependent effect, where two-day-old mice were bacteremic as early as 2-hours post-infection, with rapid systemic dissemination to tissues including the brain, liver, lungs, and spleen. Interestingly, only the liver and lungs revealed inflammation following histopathological analysis. We then used this model to assess the utility of passive immunization by transferring immune K. pneumoniae rabbit antisera to infected neonates pre- and post-lethal challenge. We demonstrated that the passive immunization model is an effective tool, as the transfer of rabbit antisera improved the survival rate of K. pneumoniae-infected neonates. Finally, we determined the suitability of a maternal immunization model by vaccinating dams with either heat-killed K. pneumoniae or an O polysaccharide (OPS) glycoconjugate vaccine and assessing survival rates and bacterial burden in neonates following lethal challenge. Our maternal immunization model provided significant protection, with neonates immunized with the heat-killed vaccine showing enhanced survival and reduced bacterial burden when compared to nonimmune neonates. Taken together, we successfully generated and characterized a novel and reproducible mouse model for K. pneumoniae neonatal sepsis. This work not only provided a much-needed preclinical platform but also identified protective readouts, via passive and maternal immunization, to aid in evaluating vaccine efficacy against K. pneumoniae neonatal sepsis.