The zebrafish has become a powerful model organism to study host-pathogen interactions. Here, we developed a zebrafish model to dissect the innate immune response toLegionella pneumophiladuring infection. We show thatL.pneumophilacause zebrafish larvae death in a dose dependent manner. Additionally, we show that macrophages are the first line of defence and cooperate with neutrophils to clear the infection. Immunocompromised humans have an increased propensity to develop pneumonia, similarly, when either macrophages or neutrophils are depleted, these “immunocompromised” larvae become lethally sensitive toL.pneumophila. Also, as observed in human infections, the adaptor signalling molecule Myd88 is not required to control disease in the larvae. Furthermore, proinflammatory cytokine genesil1βandtnf-αwere upregulated during infection, recapitulating key immune responses seen in human infection. Strikingly, we uncovered a previously undescribed infection phenotype in zebrafish larvae, whereby bloodborne, wild typeL.pneumophilainvade and grow in the larval yolk region, a phenotype not observed with a type IV secretion system deficient mutant that cannot translocate effectors into its host cell. Thus, zebrafish larva represents an innovativeL.pneumophilainfection model that mimics important aspects of the human immune response toL.pneumophilainfection and will allow the elucidation of mechanisms by which type IV secretion effectors allowL.pneumophilato cross host cell membranes and obtain nutrients from nutrient rich environments.