The human pathogen Staphylococcus aureus is considered mainly an extracellular, opportunistic pathogen, yet the bacterium is able to survive within and escape from host cells, including macrophages. An agr/ sae mutant of strain USA300 is unable to escape from human macrophages but can replicate and survive within macrophages. We questioned whether such “„non-toxic“” S. aureus resembles the less pathogenic coagulase-negative Staphylococcal species (CoNS) like S. carnosus, S. lugdunensis, S. capitis, S. warneri or S. pettenkoferi. We show that in contrast to the “„non-toxic“” S. aureus strains, the CoNS species are efficiently killed within 24 h post-infection in the macrophage-like THP-1 cells or in human primary macrophages. Bacterial persistence of “„non-toxic“” S . aureus or CoNS induced IL-1ß release but no cell-death. Mutations in genes coding for katalase, copprer transport or the regulatory system GraRS or SigB did not impact bacterial survival in THP-1 cells. Deletion of the superoxide dismutases sodA and sodM impaired S. aureus survival in human primary macrophages but not in THP-1 cells. However, expression of the S. aureus specific sodM in S. epidermidis was not sufficient to protect this species from being killed in THP-1 cells. Thus, at least in those cells better bacterial survival of S. aureus could not be linked to higher protection from ROS. However, “„non-toxic“” S. aureus was found to be insensitive to pH, whereas S. epidermidis was protected when phagosomal acidification was inhibited. Thus, species differences seem to be linked to different sensitivity to acidification.