Physician well-being has become an important area of interest given that reduced well-being can have a negative effect on patient outcomes. However, research has predominantly focused on impairment thus studies addressing physicians' positive functioning are limited. The purpose of this two-phase, mixed methods study was to investigate the well-being and self-regulation capacity of physicians using a positive psychology lens. In Phase 1, 132 physicians (n = 40 physicians; n = 92 resident physicians) completed online questionnaires to assess their levels of psychological and affective well-being and self-regulation capacity. Selected based on Phase 1 data, 12 physicians then took part in an in-depth individual interview in Phase 2 to discuss their experiences of psychological well-being and self-regulation. Results of Phase 1 showed that physicians and resident physicians had moderate and high levels of self-regulation capacity, respectively. While both groups reported high levels of psychological well-being, they had average levels of positive and negative affect. MANOVAs confirmed the hypothesis that high self-regulating physicians and resident physicians would have higher levels of psychological well-being and positive affect compared to those with lower levels. However, those with higher self-regulation capacity did not have lower negative affect, nor did physicians have significantly higher levels of psychological and affective well-being than resident physicians. Regression analyses confirmed the hypothesis that a significant amount of variance in levels of psychological well-being would be explained by self-regulation capacity. There was a particularly strong relationship between self-regulation capacity and the dimensions of purpose in life and environmental mastery, which suggests that physicians who effectively self-manage may be better able to preserve a sense of purpose and an adequate work-life balance in their daily life. A qualitative content analysis of the Phase 2 qualitative data revealed that physicians had both high and low functioning experiences of psychological well-being across the dimensions of self-acceptance, positive relations with others, environmental mastery, and autonomy. They, however, reported high functioning for the dimensions of personal growth and purpose in life. Their experiences also varied based on their professional and personal life contexts, with work-life balance emerging as a prevalent theme. Physicians' self-regulation experiences involved individualized preparation, performance, and evaluation processes that were perceived to influence their well-being. Results of a composite analysis suggest that the development of effective self-regulation skills could be one way to help physicians achieve satisfactory levels of well-being.