Significant mortality of Crassostrea gigas juveniles is observed systematically every year worldwide. Pacific Oyster Mortality Syndrome (POMS) is caused by Ostreid Herpesvirus 1 (OsHV-1) infection leading to immune suppression, followed by bacteraemia caused by a consortium of opportunistic bacteria. Using an in-situ approach and pelagic chambers, our aim in this study was to identify pathogen dynamics in oyster flesh and in the water column during the course of a mortality episode in the Mediterranean Thau lagoon (France). OsHV-1 concentrations in oyster flesh increased before the first clinical symptoms of the disease appeared, reached maximum concentrations during the moribund phase and the mortality peak. The structure of the bacterial community associated with oyster flesh changed in favour of bacterial genera previously associated with oyster mortality including Vibrio, Arcobacter, Psychrobium, and Psychrilyobacter. During the oyster mortality episode, releases of OsHV-1 and opportunistic bacteria were observed, in succession, in the water surrounding the oyster lanterns. These releases may favour the spread of disease within oyster farms and potentially impact other marine species, thereby reducing marine biodiversity in shellfish farming areas.