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We explored the possibility of a relationship between mindfulness and burnout among Chinese civil pilots, and investigated the mediating effects of fatigue and proactive coping in this relationship. Participants were 319 civil pilots employed by China Southern Airlines, who completed a survey. Structural equation modeling was used to test the hypothesized parallel mediation model. Results show that the direct effect of mindfulness on burnout was not significant, but mindfulness had an important preventative effect on burnout. Furthermore, fatigue and proactive coping completely mediated the effect of mindfulness on burnout. Consequently, our findings corroborate the predictive role of fatigue and proactive coping in mediating the indirect effect that mindfulness exerted on burnout. Theoretical implications and practical recommendations for pilots’ mindfulness training practice and fatigue risk management systems are discussed.