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During the late 3 rd millennium BCE, the Eastern Mediterranean and Near East witnessed societal changes in many regions, which are usually explained with a combination of social and climatic factors. 1-4 However, recent archaeogenetic research forces us to rethink models regarding the role of infectious diseases in past societal trajectories. 5 The plague bacterium Yersinia pestis, which was involved in some of the most destructive historical pandemics, 5-8 circulated across Eurasia at least from the onset of the 3 rd millennium BCE, 9-13 but the challenging preservation of ancient DNA in warmer climates has restricted the identification of Y. pestis from this period to temperate climatic regions. As such, evidence from culturally prominent regions such as the Eastern Mediterranean is currently lacking. Here, we present genetic evidence for the presence of Y. pestis and Salmonella enterica, the causative agent of typhoid/enteric fever, from this period of transformation in Crete, detected at the cave site Hagios Charalambos. We reconstructed one Y. pestis genome that forms part of a now-extinct lineage of Y. pestis strains from the Late Neolithic and Bronze Age that were likely not yet adapted for transmission via fleas. Furthermore, we reconstructed two ancient S. enterica genomes from the Para C lineage, which cluster with contemporary strains that were likely not yet fully host adapted to humans. The occurrence of these two virulent pathogens at the end of the Early Minoan period in Crete emphasizes the necessity to re-introduce infectious diseases as an additional factor possibly contributing to the transformation of early complex societies in the Aegean and beyond., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)