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Background: A consensual definition of occupational burnout is currently lacking. We aimed to harmonize the definition of occupational burnout as a health outcome in medical research and to reach a consensus on this definition within the Network on the Coordination and Harmonisation of European Occupational Cohorts (OMEGA-NET). Methods: First, we performed a systematic review in MEDLINE, PsycINFO and EMBASE (January 1990 to August 2018) and a semantic analysis of the available definitions. We used the definitions of burnout and burnout-related concepts from the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to formulate a consistent harmonized definition of the concept. Second, we sought to obtain consensus on the proposed definition using the Delphi technique. Results: We identified 88 unique definitions of burnout and assigned each of them to one of the 11 original definitions. The semantic analysis yielded a semantic proposal, formulated in accordance with SNOMED-CT as follows: “In a worker, occupational burnout or occupational physical AND emotional exhaustion state is an exhaustion due to prolonged exposure to work-related problems”. A panel of 50 experts (researchers and healthcare professionals with an interest for occupational burnout) reached consensus on this proposal at the second round of the Delphi, with 82% of experts agreeing on it. Conclusion: This study resulted in a harmonized definition of occupational burnout approved by experts from 29 countries within the OMEGA-NET. Future research should address the reproducibility of the Delphi consensus in a larger panel of experts, representing more countries, and examine the practicability of the definition.