Self-compassion has shown promise as an adaptive resource for coping with uncertainties and challenges. This study examined the relationship between self-compassion and professional wellbeing (work engagement, exhaustion, and professional life satisfaction) of physicians, who frequently face uncertainties and challenges in their clinical practice. Fifty-seven practicing physicians in Canada participated in the study. Overall, 65% of the participants were female; 47% were in the early-career stage; 49% were family medicine (FM) physicians, with the rest being non-FM specialists. It was hypothesized that (a) self-compassionate physicians would experience greater work engagement and less exhaustion from work than physicians reporting lower self-compassion and (b) self-compassionate physicians would experience greater professional life satisfaction through their greater work engagement and less exhaustion than physicians reporting lower self-compassion. Sequential regression analyses were performed. The results confirmed the hypothesized associations, indicating that self-compassionate physicians experienced more positive work engagement, felt less emotionally, physically, and cognitively exhausted due to work demands, and were more satisfied with their professional life than physicians who exhibited less compassion toward themselves in uncertain and challenging times. Future studies are needed to determine optimal ways to support practicing physicians and medical trainees in becoming more self-compassionate for their enhanced wellbeing and, ultimately, for the provision of effective patient care.