Vibrio aestuarianus infection in oyster populations causes massive mortality, resulting in losses for oyster farmers. Such dynamics result from host-pathogen interactions and contagion through water-borne transmission. To assess the spatiotemporal spread of V. aestuarianus infection and associated oyster mortality at a bay scale, we built a mathematical model informed by experimental infection data at 2 temperatures and spatially dependent marine connectivity of oyster farms. We applied the model to a real system and tested the importance of each factor using a number of modelling scenarios. Results suggest that introducing V. aestuarianus in a fully susceptible adult oyster population in the bay would lead to the mortality of all farmed oysters over 6 to 12 mo, depending on the location in which infection was initiated. The effect of temperature was captured by the basic reproduction number (R0), which was >1 at high seawater temperatures, as opposed to values <1 at low temperatures. At the ecosystem scale, simulations showed the existence of long-distance dispersal of free-living bacteria. The western part of the bay could be reached by bacteria originating from the eastern side, though the spread time was greatly increased. Further developments of the model, including the consideration of the anthropogenic movements of oysters and oyster-specific sensitivity factors, would allow the development of accurate maps of epidemiological risks and help define aquaculture zoning.