PurposeTo explore distress in the medical profession and how it was highlighted by the ongoing COVID-19 pandemic. The term "orientational distress" was developed to name the experience of a breakdown in the patterns of moral self-understanding and one's capacity to navigate professional responsibilities. MethodThe Enhancing Life Research Laboratory at the University of Chicago convened a 5-session online workshop (total 10 hours, May-June 2021) to explore orientational distress and to promote collaboration between academics and physicians. Sixteen participants from Canada, Germany, Israel, and the United States engaged in discussions of the conceptual framework and toolkit to address orientational distress within institutional settings. The tools included 5 dimensions of life, 12 dynamics of life, and the role of counterworlds. Follow-up narrative interviews were transcribed and coded using a consensus-based iterative process. ResultsParticipants reported that the concept of orientational distress helped explain their professional experiences better than burnout or moral distress. Moreover, participants strongly endorsed the project's supporting thesis that collaborative work on orientational distress and the tools provided in the research laboratory had a specific intrinsic value and provided benefits not found in other support instruments. ConclusionsOrientational distress compromises medical professionals and threatens the medical system. Next steps include the dissemination of materials from the Enhancing Life Research Laboratory to more medical professionals and medical schools. In contrast to burnout and moral injury, the concept of orientational distress may better enable clinicians to understand and more fruitfully navigate the challenges of their professional situations.