Background: Physical activity (PA)-related mood improvement is important because it positively affects predictors of weightmanagement behaviors. Methods: Decline in PA, mood, and exercise self-efficacy after an initial 6 months of gains were assessed in 93 women in a behavioral obesity treatment. Results: Reduction in change in PA during months 6 to 24, but not actual PA, significantly predicted increased negative mood. For participants whose negative mood increased, their 7 days per week PA regimens were reduced by ~2.5 days per week versus ~1 day per week without an increase. Exercise self-efficacy significantly mediated the PA-mood change relationship. Conclusions: Mood-related benefits of sustaining PA beyond initial treatment months were clarified.