Diel-cycling hypoxia and pH co-occur in shallow waters world-wide. Eutrophication tends to increase the occurrence and severity of diel cycles. We used laboratory experiments to investigate effects of diel-cycling DO and pH on acquisition and progression of infections by Perkinsus marinus, the protistan parasite which causes Dermo disease, as well as hemocyte activity, growth, and feeding in the eastern oyster, Crassostrea virginica, an important estuarine species. Diel-cycling DO increased P. marinus infection and cycling DO and pH stimulated hemocyte activity and reduced oyster growth. However, ambient environmental conditions and oyster age modulated some of these effects. Co-varying DO and pH cycles sometimes had less severe effects than either cycle independently. Oysters may acclimate to, or compensate for, effects of cycling conditions on growth. Variation in magnitude and spatial extent of cycling conditions is an important consideration when choosing restoration sites, as severe cycling conditions may hinder re-establishment of estuarine populations.