Background <p>Medicine as a profession is steeped in meaning. Spiritual and religious practices are one way in which providers make meaning in their lives and therefore in their work. Recent attention has focused on the religious and spiritual commitments of physicians as they relate to topics such as&#xa0;self-care, physician conscience, and how these beliefs impact clinical practice.</p> Objective <p>To assess the religious and spiritual beliefs of internal medicine physicians and the degree to which these beliefs are associated with burnout.</p> Design <p>A national, cross-sectional survey of internal medicine physicians.</p> Participants <p>Between June 2023 and May 2024, surveys were sent to 1421 randomly selected internal medicine physicians practicing in the USA identified through the American Medical Association membership database.</p> Main Measures <p>The survey included 42 questions designed to assess factors hypothesized to influence physician well-being and professional burnout. We also collected physician demographic data and assessed burnout via the Maslach Burnout Inventory.</p> Key Results <p>A total of 629 (44.3%) completed a survey. Almost 70% of the general internists who responded endorsed belief in God or a higher power, and approximately half endorsed praying privately at least once a week at a place other than a place of worship and had a belief in life after death. Black respondents had four times greater odds of believing in God compared with non-Black respondents (OR = 4.14, 95% CI = 1.24 – 13.84, <i>P</i> = 0.02). A total of 61% of respondents were classified as having at least one manifestation of burnout. Having a religious affiliation was protective against one manifestation of burnout (OR = 0.43, 95% CI = 0.26 – 0.72, <i>P</i> = 0.001).</p> Conclusions <p>Religion and spirituality are prominent and important aspects in the lives of many practicing internal medicine physicians in the USA and may impact physician well-being.</p>