In a retrospective analysis of 24,552 US adults, including 812 patients with rheumatoid arthritis, higher oxidative balance—measured by the oxidative balance score (OBS)—was associated with lower all-cause mortality, while greater systemic inflammation—measured by the systemic inflammation response index (SIRI)—was associated with higher mortality. Each 1-point increase in OBS corresponded to a 4% reduction in mortality risk, whereas each 1-unit increase in SIRI was linked to a 14% increase. Patients with high inflammation and low oxidative balance had the worst survival, while those with low inflammation and high oxidative balance had the best outcomes. Mediation analysis suggested that antioxidant status may reduce mortality risk in part by attenuating systemic inflammation.