UNLABELLED: The oral microbiome is a complex community that matures with dental development and is recognized as a risk factor for systemic disease. Despite the oral cavity having a substantial microbial burden, healing of superficial oral wounds occurs quickly and with little scarring. By contrast, creation of an oro-nasal fistula (ONF), often occurring after surgery to correct a cleft palate, is a significant wound healing challenge. METHODS: In this study, we characterized the changes in the oral microbiome of mice following a freshly inflicted wound in the oral palate that results in an open and unhealed ONF. RESULTS: Creation of an ONF in mice significantly lowered oral microbiome alpha diversity, with concurrent blooms of CONCLUSIONS: An ONF in the murine palate leads to a dysbiotic oral microbiome and a bloom of opportunistic pathogens that may prevent ONF healing. Delivery of therapeutics that accelerate ONF healing might restore oral microbiome diversity and inhibit blooms of opportunistic pathogens.