ObjectiveTo investigate the relationship between burn-out and spiritual health among medical doctors.DesignSystematic literature review and narrative synthesis of cross-sectional studies.SettingAny setting, worldwide.Data sourcesFive databases were searched from inception to March 2022, including Medline, Embase, PsycINFO, Scopus and Web of Science.Eligibility criteriaAny study design that involved medical doctors (and other healthcare staff if assessed alongside medical doctors), that measured (in any way) both burn-out (or similar) and spiritual health (or similar) medical doctors.Data extraction and synthesisAll records were double screened. Data extraction was performed by one reviewer and a proportion (10%) checked by a second reviewer. Quality was assessed using the Appraisal of Cross-sectional Studies tool. Due to the heterogeneity of the included studies, a narrative review was undertaken without a meta-analysis.ResultsSearches yielded 1049 studies. 40 studies met eligibility criteria and were included in this review. Low reported levels of spirituality were associated with high burn-out scores and vice versa. Religion was not significantly associated with lower levels of burn-out. Few studies reported statistically significant findings, few used validated spiritual scores and most were vulnerable to sampling bias.ConclusionsPublished research suggests that burn-out is linked to spiritual health in medical doctors but not to religion. Robust research is needed to confirm these findings and develop effective interventions.PROSPERO registration numberCRD42020200145.