Aquaculture activity is affected by various environmental factors, including water salinity and high temperatures. The present study investigated the impact of using varying water salinity (0, 5, 10, 15 and 20 ppt) on the growth behavior, immune responses and antioxidative responses of common carp. Fish were raised under optimal conditions except for water salinity for 8 weeks; fish were then subjected to high-temperature stress (32 °C) for 48 h. The results indicated a reduced final weight (FBW), weight gain (WG), specific growth rate (SGR), condition factor (CF), feed intake and feed efficiency ratio (FER) in common carp reared in 15 and 20 ppt (p < 0.05). The lowest FBW, WG, SGR, CF, feed intake and FER values were observed in fish reared in 20 ppt water salinity (p < 0.05). In gills, the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were markedly decreased, but malondialdehyde (MDA) levels increased in fish challenged with 15 and 20 ppt before they were subjected to heat stress (p < 0.05). After heat stress, the SOD, CAT and GPx were decreased, and the MDA increased in fish reared in varying salinity levels (p < 0.05). Before heat stress, the intestinal SOD, CAT and GPx markers were decreased by 15 and 20 ppt, while the MDA level was increased by 15 and 20 ppt (p < 0.05). Generally, heat stress lowered the SOD, CAT and GPx activity in the intestines and liver tissues but increased MDA levels in common carp stressed by varying salinity levels (p < 0.05). The most decreased lysozyme activity, SOD, CAT and GPx and increased MDA levels were observed in common carp exposed to 20 ppt before and after heat stress (p < 0.05). After heat stress, fish exposed to 15 and 20 ppt had lower NBT than the remaining groups, and fish exposed to 20 ppt had the lowest values (p < 0.05). Overall, the heat stress markedly suppressed the antioxidant and immune responses of common carp reared in hypersalinity conditions.