Oyster diseases have major consequences on fisheries and aquaculture. In France, young Pacific oysters Crassostrea gigas are severely hit by the ostreid herpesvirus, whereas adults suffer mortalities presumably caused by pathogenic bacteria. Here we investigated the origin and spread of mortalities that affect both young and adult oysters, and we identified and compared their risk factors. Mortality was monitored in 2 age classes of oysters deployed in early spring at 39 sites spread over a 37 km2 surface area inside and outside of shellfish farms. Environmental data obtained from numerical modelling were used to investigate risk factors. Mortality of young oysters associated with ostreid herpesvirus occurred in the oyster farming area. Hydrodynamic connectivity with oyster farms was associated with higher mortality risk, whereas chlorophyll a concentration was associated with a lower risk. Adult oysters experienced 2 mortality events that were associated with different risk factors. The first event, which occurred after deployment and was probably caused by endogenous pathogens, was mainly associated with connectivity to channel rivers and salinity. The second mortality event observed at the end of the summer was mainly associated with connectivity to oyster farms, suggesting pathogen transmission. The risk factors involved in young and adult oyster mortalities were partly different, reflecting distinct origins. Connectivity with oyster farms is a mortality risk factor for both young and adult oysters; thus, disease management strategies that focus on oyster farming areas will impact overall disease risk.