Background <p>To investigate the relationship between mindfulness and burnout in physicians and its underlying mechanisms.</p> Methods <p>Study 1 employed a multiverse-style analysis based on a large sample of 8,462 physicians to examine the robust relationship between mindfulness(MAAS) and burnout(MBIES). Study 2 conducted a 21-day intensive longitudinal assessment on 471 physicians to explore the internal mechanisms by which mindfulness affects burnout.</p> Results <p>Study 1 found that the negative association between mindfulness and burnout is robust. Study 2 discovered that Perceived Organizational Support(POS) and Psychological Safety(PS) play a sequential mediating role in the effect of mindfulness on burnout.</p> Conclusions <p>These findings provide a theoretical basis for formulating interventions at the organizational level and have important practical and theoretical significance for optimizing physicians’ work environments and improving the medical quality.</p> Clinical trial number <p>Not applicable.</p>