Ocean acidification and heavy metal pollution are two global marine environmental problems, both of which have influences on the survival of marine organisms and the health of ecosystems. As a widely distributed glial zooplankton in the ocean, Aurelia coerulea plays an important role in biogeochemical cycle of important elements, such as carbon, nitrogen, and phosphorus. Many previous studies have reported the growth and population abundance of A. coerulea are susceptible to changes of the marine environment. In this study, the physiological response of A. coerulea ephyrae to ocean acidification (pH 8.1 and pH 7.6) and Cu²⁺ (0, 10 μg/L and 25 μg/L) stress was analyzed by measuring the activities of physiological metabolic enzymes including catalase (CAT), superoxide dismutase (SOD), Ca²⁺-ATPase, as well as respiration rates, pulsation rates and bell diameter of A. coerulea. The results showed that ocean acidification and Cu²⁺ stress had different effects on physiological indices of A. coerulea ephyrae. Cu²⁺ exposure can significantly inhibit the activities of CAT and Ca²⁺-ATPase, as well as the pulsation rates and growth rate of A. coerulea ephyrae. Besides, Cu²⁺ exposure can also lead to a significant increase in SOD activity and respiratory rate. While copper pollution might affect the swimming behavior of A. coerulea, leading to the significant decline in their predation ability and ontogeny. Furthermore, a negative correlation was observed between the bell diameter and Cu²⁺ concentration. Seawater acidification had an inhibitory effect on activity of CAT, SOD, and Ca²⁺-ATPase, as well as growth of A. coerulea ephyrae, and promoted its respiration. However, when A. coerulea ephyrae were exposed to co-exposure of seawater acidification and Cu²⁺, there were significant antagonistic effect between seawater acidification and Cu²⁺ on the growth and respiration of A. coerulea ephyrae. Our study indicates that the adaptability of A. coerulea ephyrae to copper pollution is enhanced with the background of ocean acidification. The different physiological effects of ocean acidification and Cu²⁺on A. coerulea identified in current study may lead to changes in marine biodiversity and ecosystems in the future.