Staphylococcus aureus has two superoxide dismutases (SODs), encoded by the sodA and sodM genes, which inactivate harmful superoxide radicals () encountered during host infection or generated from aerobic metabolism. The transcriptional start sites have been mapped and expression analysis on reporter fusions in both genes has been carried out. Under standard growth conditions, manganese (Mn), a mineral superoxide scavenger, elevated total SOD activity but had no effect on the transcription of either gene. Transcription of sodA and sodM was most strongly induced by either internally or externally generated , respectively. Sensitivity to internally generated was linked with SodA deficiency. Mn supplementation completely rescued a sodA mutant when challenged by internally generated , and this was growth-phase-dependent. Sensitivity to externally generated stress was only observed in a sodA sodM mutant and was Mn-independent. In a mouse abscess model of infection, isogenic sodA, sodM and sodA sodM mutants had reduced virulence compared to the parental strain, showing the importance of the enzymic scavenging system for the survival of the pathogen.