Increasing global temperature is causing water temperatures to increase, potentially leading to metabolic disorders in fish. The Xingguo red carp (Cyprinus carpio var. singuonensis) is an economically important fish in China; however, studies on its adaptation mechanism to high temperatures are relatively few. To analyze the changes in physiological regulation under heat stress, the present study simulated an acute high-temperature environment and cooling environment, and gill tissues of Xingguo red carp at different temperature levels (28 ℃ and 38 ℃) were examined. The results of enzyme activity indices showed that malondialdehyde (MDA) increased significantly and catalase (CAT) content decreased significantly after high temperature stress, whereas no significant difference was observed in glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD). The SOD content decreased significantly after cooling, and the rest of the indicators were not significantly different. Using transcriptome sequencing analysis, 2643 differentially expressed genes (DEGs) were screened for differential genes between the high-and normal-temperature groups, of which 1,401 DEGs were upregulated and 1,242 were downregulated in Xingguo Red Carp. A total of 2396 DEGs were screened to compare the cooled and high-temperature groups, including 936 upregulated DEGs and 1460 downregulated DEGs. In comparing the cooled and normal-temperature groups, a total of 908 DEGs were screened, of which 300 DEGs were upregulated and 608 DEGs were downregulated. Meanwhile, the activation and involvement of DEGs in immune and apoptosis-related pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, such as endoplasmic reticulum protein processing, IL-17 signaling pathway, NF-κB signaling pathway, p53 signaling pathway, and apoptosis. Within these pathways, key signaling factors such as HSPs, IL-1β, IL-8, p53, Caspase-3, and HIF-1α showed different expression trends. The results showed that Xingguo red carp responds to high-temperature stress stimuli during high temperature stress by positively upregulating gene expression. However, the expression of Xingguo red carp immune-related genes and pathways were downregulated or suppressed, leading to suppression of the immune system, while apoptosis regulation was blocked, preventing the effective removal of abnormal and damaged cells. Furthermore, no signs of hypoxia existed. Following cooling recovery, the stress of the Xingguo red carp decreased. The immune response of Xingguo red carp was activated, and the inflammatory symptoms were reduced, but they did not recover completely. The symptoms of hypoxia returned to normal. These two levels were used to systematically investigate the physiological regulation mechanism of Xingguo red carp in high temperature environment. This study provides valuable information on how aquatic species adapt to high-temperature environments.