The effect of temperature on cerebral injury during hypothermic circulatory arrest (HCA) has never been specifically studied. This study aimed to compare the effects of two different temperatures used for HCA on the degree of brain injury in pig models. Thirteen pigs were randomly assigned to a deep hypothermic circulatory arrest (DHCA) group (n = 5), moderate hypothermic circulatory arrest (MHCA) group (n = 5), or control group (n = 3). No significant differences in immunohistochemical assay results, including Bax, Bcl-2, and Caspase 3 staining, and a TUNEL assay, were observed between the DHCA and MHCA groups. Furthermore, no significant difference was found for biomarkers of brain injury (Soluble protein-100B) between the two experimental groups. Similarly, no significant difference was observed in the trend of changes in inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-2, and IL-6, between the two groups (p > 0.05). However, coagulation factors, including FXI and FVII, were different between the DHCA and MHCA groups (p < 0.05). Therefore, it can be concluded that MHCA does not increase the risk of cerebral injury. Considering the adverse effects of DHCA on the coagulation system, MHCA is more suitable for current clinical practice.