The consequences of emerging marine diseases on the evolutionary trajectories of affected host populations in the marine realm are largely unexplored. Evolution in response to natural selection depends on the genetic variation of the traits under selection and the interaction of these traits with the environment (GxE). However, in the case of diseases, pathogen genotypes add another dimension to this interaction. Therefore, the study of disease resistance needs to be extended to the interaction of host genotype, pathogen genotype and environment (GxGxE). In this study, we used a full-sib breeding design crossing two genetically differentiated populations of the Pacific oyster Crassostrea gigas (Thunberg, 1793), to determine the influence of host genotype, pathogen genotype and temperature on disease resistance. Based on a controlled infection experiment on two early life stages, that is, D-larvae and Pediveliger larvae at elevated and ambient water temperatures, we estimated disease resistance to allopatric and sympatric Vibrio sp. by measuring survival and growth within and between genetically differentiated oyster populations. In both populations, survival was higher upon infection with sympatric Vibrio sp., indicating that disease resistance has a genetic basis and is dependent on host genotype. In addition, we observed a significant GxGxE effect in D-larvae, where contrary to expectations, disease resistance was higher at warm than at cold temperatures. Using thermal reaction norms, we could further show that disease resistance is an environment dependent trait with high plasticity, which indicates the potential for a fast acclimatization to changing environmental conditions. These population-specific reaction norms disappeared in hybrid crosses between both populations which demonstrates that admixture between genetically differentiated populations can influence GxGxE interactions on larger scales.