The human opportunistic pathogen Staphylococcus aureus has developed multiple strategies to adapt to various environments, to fight and escape the immune system, to spread and persist in host tissues. It is responsible for numerous diseases ranging from benign skin infections to more serious such as endocarditis or septicemia. The pathogenicity is due to the production of a multitude of virulence factors, whose synthesis is finely regulated by a combination of regulatory proteins and small non-coding RNAs (sRNAs). Our study reveals an unexpected function of an atypical sRNA, RsaC, which is at the heart of networks controlling defence responses to oxidative stress, manganese import and nutrition immunity. This work highlights a novel mechanism required for S. aureus to survive into its host.