Background: The widespread use of social media represents an unprecedented opportunity for health promotion. We have more information and evidence-based health related knowledge, for instance about healthy habits or possible risk behaviors. However, these tools also carry some disadvantages since they also open the door to new social and health risks, in particular during health emergencies. This systematic review aims to study the determinants of infodemics during disease outbreaks, drawing on both quantitative and qualitative methods.Methods: We searched research articles in PubMed, Scopus, Medline, Embase, CINAHL, Sociological abstracts, Cochrane Library, and Web of Science. Additional research works were included by searching bibliographies of electronically retrieved review articles.Results: Finally, 42 studies were included in the review. Five determinants of infodemics were identified: (1) information sources; (2) online communities' structure and consensus; (3) communication channels (i.e., mass media, social media, forums, and websites); (4) messages content (i.e., quality of information, sensationalism, etc.,); and (5) context (e.g., social consensus, health emergencies, public opinion, etc.). Studied selected in this systematic review identified different measures to combat misinformation during outbreaks.Conclusion: The clarity of the health promotion messages has been proven essential to prevent the spread of a particular disease and to avoid potential risks, but it is also fundamental to understand the network structure of social media platforms and the emergency context where misinformation might dynamically evolve. Therefore, in order to prevent future infodemics, special attention will need to be paid both to increase the visibility of evidence-based knowledge generated by health organizations and academia, and to detect the possible sources of mis/disinformation.