Legionella pneumophila is an intracellular bacterium that has adapted to infect human hosts, resulting in the onset of severe atypical pneumonia. Previously we identified a eukaryotic-type ecto-nucleoside triphosphate diphosphohydrolase (NTPDase), Lpg1905, from L. pneumophila. The enzymatic function of Lpg1905 was required for optimal intracellular replication and virulence in a mouse lung infection model. In this study, we characterized the activity of Lpg0971, a second eukaryotic-type NTPDase from L. pneumophila. We observed that recombinant Lpg0971 exhibited divalent cation preference for manganese (II) ions and hydrolysed ATP only. Similar to lpg1905, an lpg0971 mutant carrying pMIP was attenuated in a mouse lung infection model and impaired for replication in human macrophages and amoebae. However, complementation with either lpg1905 or lpg0971 restored intracellular replication, suggesting functional redundancy between the two enzymes. Unlike many eukaryotic-type proteins from L. pneumophila, neither Lpg1905 nor Lpg0971 were translocated into the host cell by the Dot/Icm type IV secretion system using either CyaA-fusions or BlaM-fusions. This suggests that their activity is restricted to the Legionella-containing vacuole. In summary, the ability of L. pneumophila to replicate in eukaryotic cells relies in part on the ability of the pathogen to hydrolyse ATP within an intracellular compartment.