Objective To investigate the effect of ultrasound-guided type II pectoral nerve block combined with serratus anterior plane block on stress response and postoperative recovery in patients undergoing general anesthesia for radical mastectomy.Methods From January 2023 to January 2024, 102 female patients with breast cancer who received radical mastectomy in the Maternity and Child Care Center of Qinhuangdao were selected. They were randomly assigned to an observation group consisting of 51 cases and a control group comprising 51 cases. All patients underwent radical mastectomy, together with ipsilateral axillary lymph node dissection and pectoral intramuscular lymph node dissection. The control group received general intravenous anesthesia during the operation, while the observation group received ultrasound-guided type II pectoral nerve block combined with serratus anterior plane block before general intravenous anesthesia. The mean arterial pressure (MAP) and heart rate (HR) of the two groups before anesthesia (T₀), after skin incision (T₁), and 15 minutes after surgery (T₂) were compared. The intraoperative remifentanil dosage, duration of surgery, postoperative extubation time, and recovery time were recorded for both groups. The postoperative levels of prostaglandin E2 (PGE2), norepinephrine (NE), and catalase (CAT), as well as the incidence of adverse reactions, were compared between the two groups.Results Repeated measures analysis of variance was used to compare the MAP and HR between the observation and control groups at T₀, T₁, and T₂, which showed that MAP and HR were significantly different across the time points (P < 0.05) but did not differ between the observation group and the control group (P > 0.05). There was a statistically significant difference in the change trends of MAP and HR between the two groups (P < 0.05), where they were lower in the observation group than in the control group. There was no difference in duration of surgery, postoperative extubation time, or recovery time between the two groups (P > 0.05). Comparison of pain scores between the observation group and the control group at 4 hours, 24 hours, and 72 hours after surgery was conducted using the repeated measures analysis of variance. The results revealed that there was a statistically significant difference in pain scores among different time points (P < 0.05) and the pain scores were different between the observation group and the control group (P < 0.05). The difference in the change trend of pain scores between the two groups was statistically significant (P < 0.05). The differences of PGE2, NE, and CAT levels before and after surgery in the observation group were lower than those in the control group (P < 0.05). There was no difference in the incidence of adverse reactions between the two groups (P >0.05).Conclusion Ultrasound-guided type II pectoral nerve block combined with serratus anterior plane block during general anesthesia for radical mastectomy can help alleviate postoperative pain and stress responses, while demonstrating good postoperative recovery and safety.