Environmental change in the marine realm has been accompanied by emerging diseases as new pathogens evolve to take advantage of hosts weakened by environmental stress. Here we investigated how an exposure to reduced seawater pH influenced the response of the oyster Crassostrea gigas to an infection by the Ostreid herpesvirus type I (OsHV-1). Oysters were acclimated at pH 8.1 or pH 7.8 and then exposed to OsHV-1. Their survival was monitored and oyster tissues were sampled for biochemical analyses. The survival of oysters exposed to OsHV-1 at pH 7.8 was lower (33.5%) than that of their counterparts at pH 8.1 (44.8%) whereas levels of OsHV-1 DNA were similar. Energetic reserves, fatty acid composition and prostaglandin levels in oyster did not vary consistently with pH, infection or their interactions. However, there was a reduction in the activities of superoxide dismutase (SOD) and nitric oxide synthase (iNOS) in oysters at low pH, which is associated with the observed difference in survival.