Given the traditional methods of treating obesity through education on controlling eating and increasing exercise have largely failed beyond the very short term, a more intensive focus on psychosocial correlates of those weight-loss behaviors has been suggested. Multiple behavioral theories incorporate self-regulation, self-efficacy, and mood; however, their interrelations and effects over both the short and long term within cognitive-behavioral obesity treatments remain unclear. Within a novel community-based program with women with obesity who had either low (n = 29) or high (n = 71) mood disturbance scores, there were significant improvements in exercise- and eating-related self-regulation and eating-related self-efficacy-primary targets of that intervention-with no significant difference in those changes by mood disturbance grouping. Changes in the summed exercise- and eating-related self-regulation scores significantly mediated relationships between changes in eating-related self-efficacy and weight (over both 6 and 12months). There were similar results with mediation assessed via the extent exercise-related self-regulation carried over to eating-related self-regulation. In both of those models a reciprocal relationship between self-regulation and self-efficacy changes was indicated. In serial multiple mediation equations, paths of changes in exercise-related self-regulation → eating-related self-regulation → eating-related self-efficacy → weight were significant. However, paths were not significant when change in self-efficacy was entered as the predictor (initial) variable. Findings suggest viability in first focusing on exercise-related self-regulation, then eating-related self-regulation, in the course of increasing self-efficacy and probabilities for inducing enough sustained weight loss to improve obesity-associated health risks. Benefits of field-based research findings generalizing to weight-management applications were suggested.