Type 2 diabetes is a chronic condition primarily self-managed by the individual. Mastery is a protective factor linked to better control of chronic conditions, effective self-management and improved medication adherence. Mastery appears increasingly important as treatment regimens and self-management demands become more complex and burdensome. Diabetes distress negatively impacts self-management, glycaemic control and treatment adherence. Understanding the relationship between diabetes distress and mastery may provide opportunities to improve condition management and adherence . This relationship may be impacted by other factors affecting the individual's perceived sense of control over their condition. This study examined the role of diabetes empowerment and depression in the relationship between diabetes distress and mastery. Data were drawn from a randomised controlled trial of 131 adults with type 2 diabetes transitioning to injection therapy. Participants completed measures of diabetes distress , mastery , depression and empowerment . Diabetes distress and depression were negatively associated with mastery, whilst diabetes empowerment was positively associated . A significant interaction effect (b = .024, t(112) = 3.79, p = <.005) confirmed the relationship between diabetes distress and mastery was moderated by depression. Findings highlight the additive deleterious effects of depression. Interventions to improve mastery among those living with type 2 diabetes should address diabetes distress and depression to optimise outcomes.