The quorum-sensing system links metabolism to virulence, in part by increasing bacterial survival during exposure to lethal concentrations of HO, a crucial host defense against . We now report that protection by surprisingly extends beyond post-exponential growth to the exit from stationary phase when the system is no longer turned on. Thus, can be considered a constitutive protective factor. Deletion of resulted in decreased ATP levels and growth, despite increased rates of respiration or fermentation at appropriate oxygen tensions, suggesting that Δ cells undergo a shift towards a hyperactive metabolic state in response to diminished metabolic efficiency. As expected from increased respiratory gene expression, reactive oxygen species (ROS) accumulated more in the mutant than in wild-type cells, thereby explaining elevated susceptibility of Δ strains to lethal HO doses. Increased survival of wild-type cells during HO exposure required , which detoxifies superoxide. Additionally, pretreatment of with respiration-reducing menadione protected Δ cells from killing by HO. Thus, genetic deletion and pharmacologic experiments indicate that helps control endogenous ROS, thereby providing resilience against exogenous ROS. The long-lived 'memory' of -mediated protection, which is uncoupled from activation kinetics, increased hematogenous dissemination to certain tissues during sepsis in ROS-producing, wild-type mice but not ROS-deficient () mice. These results demonstrate the importance of protection that anticipates impending ROS-mediated immune attack. The ubiquity of quorum sensing suggests that it protects many bacterial species from oxidative damage.