Delaware Bay oyster (Crassostrea virginica) populations are influenced by two lethal parasites that cause Dermo and MSX diseases. As part of the US National Science Foundation Ecology of Infectious Diseases initiative, a program developed for Delaware Bay focuses on understanding how oyster population genetics and population dynamics interact with the environment and these parasites to structure the host populations, and how these interactions might be modified by climate change. Laboratory and field studies undertaken during this program include identifying genes related to MSX and Dermo disease resistance, potential regions for refugia and the mechanisms that allow them to exist, phenotypic and genotypic differences in oysters from putative refugia and high-disease areas, and spatial and temporal variability in the effective size of the spawning populations. Resulting data provide inputs to oyster genetics, population dynamics, and larval growth models that interface with a three-dimensional circulation model developed for Delaware Bay. Reconstruction of Lagrangian particle tracks is used to infer transport pathways of oyster larvae and MSX and Dermo disease pathogens. Results emerging from laboratory, field, and modeling studies are providing understanding of long-term changes in Delaware Bay oyster populations that occur as the oyster population responds to climate, environmental, and biological variability.