Superoxide dismutase (SOD) is an antioxidant enzyme that acts to degrade superoxide, a major causitive factor for oxidative stress associated with cancer, cardiovascular disease, and various other ailments. Here, to assess an association between antioxidants and lifestyle factors related to cancer risk, we analyzed serum SOD activity among the subjects within a large-scale cohort study in Japan. As results, significant differences in serum SOD activity were found between the sexes (lower in males), among female age groups (lower in younger individuals), and in males with the BMI (lower in those with a high BMI). Linear increase in serum SOD activity with aging and decrease with BMI were observed in females. Significantly low SOD activity was evident in male heavy smokers. In contrast, elevation was noted in female frequent drinkers. In conclusion, our findings do suggest associations between serum SOD activity and lifestyle factors. However, for further study, establishment of a standard measurement method for SOD activity should be a high priority.