Worldwide, Klebsiella pneumoniae is an increasingly problematic opportunistic pathogen, with the emergence of carbapenem-resistant isolates of special importance. The mechanisms of virulence are poorly understood, and the current study utilized the invertebrate model Galleria mellonella to investigate facets of the virulence process. A range of UK clinical isolates and reference strains was assessed in Galleria by measuring survival as an end point. The clinical strains showed a range of virulence, with the majority of strains (68 %) causing greater than 50 % mortality at a challenge dose of 1×105 c.f.u. Three additional intermediate read-outs were developed to allow the mechanisms of virulence of Klebsiella to be dissected further. The release of lactate dehydrogenase as a marker of cell damage was the best predictor of virulence. Melanization as a marker of the insect innate immune system and ability to proliferate within Galleria as a marker of immune evasion also broadly correlated with survival but with some notable exceptions. No direct correlation was observed between virulence and either K1 or other defined capsular types, the carriage of defined virulence factors or particular functional phenotypes. Overall, the study showed that Galleria can provide significant insights into the mechanisms of virulence, and that this can be applied to the study of opportunistic human pathogens.