Haemophilus influenzae is a major causative agent of acute respiratory diseases such as otitis media and pneumonia and drives exacerbations of chronic lung conditions including in COPD and COVID19 patients. H. influenzae infections are characterized by high levels of inflammation, which causes oxidative damage to biomolecules such as methionine which is both a nutrient and essential component of proteins. Here, we have shown that H. influenzae strains possess a novel, periplasmic stress defence system that consists of one thiol-based methionine sulfoxide reductase, MsrAB, and two molybdenum-containing S-oxide reductases, MtsZ and DmsABC. Expression of this system is triggered by exposure to hypochlorite, a product of neutrophil myeloperoxidase, and the thiol-based MsrAB enzyme was required for physical resistance of the bacteria to hypochlorite. Loss of MsrAB caused a reduction in virulence and also had immunomodulatory effects (BIRC3, antimicrobial peptides), which may be linked to the ability of MsrAB to repair damage to key outer membrane proteins. In contrast, a loss of either of the Mo-containing S-oxide reductases, MtsZ and DmsABC, caused little or no apparent cellular defect invitro, but reduced bacterial survival during infections in mice and primary human epithelia by up to 3 orders of magnitude compared to the wildtype. Both MtsZ and DmsABC are able to repair damage to small molecular biomolecules (methionine, pyrimidine, NAD-precursors) that are essential nutrients for H. influenzae. In the case of MtsZ, we identified methionine sulfoxide as a major substrate, suggesting a role of this enzyme in ensuring methionine availability and in redox- balancing via the respiratory chain. Further work revealed that MtsZ and DmsABC-related components of this HOCl-inducible stress defence system are widely distributed in bacteria, and an equivalent system is also found in Escherichia coli, where six S-oxide reductases protect the bacteria from host cell-induced stress.