Background. Mental health professionals are at risk of experiencing vicarious trauma and burnout as a consequence of the nature of their work. Studies and scholars so far have demonstrated that empathy interacts directly with burnout, and they imply an interaction with vicarious trauma. However, research has paid little attention to the interplay among vicarious trauma, empathy, and burnout in mental health professionals who practice psychotherapy. This study examines the interplay between mental health professionals’ (those practicing psychotherapy) vicarious trauma and empathy and investigates the ways they contribute to burnout. Methods. The sample consisted of 214 mental health professionals (32 males and 182 females), working in the public and private sectors. Specific instruments were administered online to the sample: (a) an improvised demographic questionnaire (age, gender, education, specialty, years of experience, years of supervision); (b) the Counselor Burnout Inventory, validated for the Greek population by Kounenou et al.; (c) the Vicarious Trauma Scale; and (d) the Jefferson Scale of Physician Empathy. Results. Correlation analysis showed that empathy and vicarious trauma were positively related to burnout. Moreover, multiple regression analysis revealed that supervision, empathy, and, to a greater degree, vicarious trauma have a significant impact on burnout. Conclusion. Unlike relative research on burnout, gender and work experience did not seem to play a significant role in the prediction of burnout in the present study. Several suggestions for future studies, as well as implications for mental health practitioners, are discussed.