Over diel and seasonal time scales, estuarine organisms like the Eastern oyster, Crassostrea virginica, can simultaneously encounter multiple environmental stressors at several stages in their life cycle. While the larval stage is one of the most vulnerable life stages, the process of settlement, a close proxy for metamorphosis, is rarely studied independently as a potential bottleneck for the success of oysters under future climate change. Also, few have studied underlying mechanisms regulating changes in higher-order processes for a more holistic understanding of organismal response to future climate change. We examined effects of multiple stressors on two life stages of oysters and tracked impacts of early exposure on the physiology of later life stages. First, oyster larvae were cultured from fertilization under a factorial combination of two temperatures and two pH values: control temperature and pH, low pH, high temperature, and a multi-stressor treatment. Second, during settlement, oysters were exposed to three pH treatments representing extreme-low, low, and control pH values. Antioxidant defenses, total protein, total lipid, respiration, and growth in both experiments are compared. Increased temperature negatively affected survival early in the larval stage, while later, acidification caused an increase in oxidative stress and decrease in biomass accumulation. Studying effects of multiple environmental stressors for the most vulnerable life phases in oysters and from a holistic perspective provides an understanding of potential plasticity and tolerance to future conditions.