Human-bacterial interactions play a crucial role in several essential aspects of life. Here, we describe how a secreted protein from the skin commensal Cutibacterium acnes, RoxP, functions as a sacrificial redox effector molecule that facilitates beneficial interactions with its human host by counteracting oxidative stress and reducing stress-induced inflammation. Using a combination of structural mapping, biophysical binding studies, and in vivo experiments, we demonstrate how RoxP contributes to skin homeostasis by serving as a target for oxidative attack and influencing cytokine signaling. To our knowledge, this is the first in vivo mechanistic description of a secreted prokaryotic effector molecule modulating host redox balance through sacrificial oxidation, providing evidence of its role as a health-promoting factor.