Two cases of necrotizing soft tissue infection of the lower extremity were treated concurrently but independently. Multimodal therapy including hip joint disarticulation and hyperbaric oxygen therapy was administered, resulting in opposite outcomes: survival and death. Analysis of the relationships between patient outcome and time-course changes in serum diacron-reactive oxygen metabolites (d-ROMs; an index of oxidative stress), antioxidative potential, and cytokines revealed that serum d-ROMs levels decreased with time, but high serum levels of interleukin-10 (anti-inflammatory cytokine) persisted in the patient who died. These findings may reflect an immunosuppressive status unfavorable to infection prevention. Serum d-ROMs may be a prognostic predictor in necrotizing soft tissue infections.