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Warm season mortality, currently referred to as Sudden Unusual Mortality Syndrome (SUMS), has impacted the expansion of oyster aquaculture across the southeastern United States. This phenomenon can occur on the order of weeks and lacks an association with commonly recognized causes of farmed oyster mortality. Although prior work has identified consistent pathology associated with these events, the mechanisms contributing to pathology and the identity of potential etiological agents have remained elusive. Here we conducted a longitudinal study through a SUMS event at a commercial oyster farm in North Carolina to investigate microbial community dynamics consistent with observations of pathology. During this study, mortality of near market sized oysters exceeded 90% across the farm and, in accordance with previous observations, was characterized by epithelial cell disruption and necrosis focal to digestive diverticula. When oysters were presenting with severe pathology, there was a contraction of the microbial community composition within oyster viscera tissues, though the dominant taxa comprising the core microbiome were sustained across stages of mortality. Using seawater samples collected within the farm, we observed increases in Vibrio spp. abundances that corresponded to pathology in oysters at critical moments of disease progression and were decoupled from other microbial signatures including phytoplankton photopigments. Together, these observations further our understanding of microbial community dynamics associated with farmed oyster mortality at the farm level. • Consistent presentation of pathology in oysters prior to onset of massive mortality event. • Contraction of microbiome is associated with most severe presentations of disease in oyster tissue. • The quantification of Vibrio bacteria in the water column using ddPCR could prove useful as a sentinel signal.