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Empathy cultivates deeper interpersonal relationships and is important for socialization. However, frequent exposure to emotionally-demanding situations may put people at risk for burnout. Burnout has become a pervasive problem among medical professionals because occupational burnout may be highly sensitive to empathy levels. To better understand empathy-induced burnout among medical professionals, exploring the relationship between burnout severity and strength of empathy-related brain activity may be key. However, to our knowledge, this relationship has not yet been explored. We studied the relationship between self-reported burnout severity scores and psychological measures of empathic disposition, emotional dissonance and alexithymia in medical professionals to test two contradictory hypotheses: Burnout is explained by (1) 'compassion fatigue'; that is, individuals become emotionally over involved; and (2) 'emotional dissonance'; that is, a gap between felt and expressed emotion, together with reduced emotional regulation. Then, we tested whether increased or decreased empathy-related brain activity measured by fMRI was associated with burnout severity scores and psychological measures. The results showed that burnout severity of medical professionals is explained by 'reduced' empathy-related brain activity. Moreover, this reduced brain activity is correlated with stronger emotional dissonance and alexithymia scores and also greater empathic disposition. We speculate that reduced emotion recognition (that is, alexithymia) might potentially link with stronger emotional dissonance and greater burnout severity alongside empathy-related brain activity. In this view, greater empathic disposition in individuals with higher burnout levels might be due to greater difficulty identifying their own emotional reactions. Our study sheds new light on the ability to predict empathy-induced burnout.