The host factors that contribute to the increased susceptibility of preterm neonates to invasive candidiasis have not been fully identified. In addition, there has been a lack of suitable models to study this problem. We show that rat pups, similar to premature neonates, display increased susceptibility to experimental Candida albicans infection. Further, we find that both C. albicans and Candida parapsilosis lipase disruptant mutants exhibit decreased virulence in rat pups, demonstrating the utility of the model to evaluate the impact of specific genes in disease pathogenesis. Our findings highlight the contribution of lipases to the virulence of C. albicans and C. parapsilosis and provide a new system to study the increased susceptibility of neonates to Candida infections.