To explore the effects of the combined applications of sufentanil, butorphanol, and dexmedetomidine during laparoscopic total hysterectomy of patients on their postoperative cognitive function and serum the expressions of immunoglobulin (Ig) A, G, and M. Methods: 80 patients who wanted laparoscopic hysterectomy were selected and were randomly divided into two groups (40 cases in each group) from May 2020 to Nov. 2021. The patients in the control group were anesthetized with butofino and sufentanil, and the patients in the study group were anesthetized with dexmedetomidine on the basis of that of the patients in the control group. The cognitive function score evaluated by Mini-Mental State Examination Scale (MMSE), the analgesic effect evaluated by Visual Analogue Scale (VAS) and the sedative effect evaluated by Ramsay score at different time points after operation, the serum IgA, IgG, and IgM levels, the levels of ain mediators indexes, such as neuropeptide (NPY), substance P (SP), and dopamine (DA), and the occurrence of adverse reactions of the patients were compared between the two groups. Results: There was no significant difference in the MMSE score of the patients in 1 day before surgery and in 3 days after surgery between the two groups (P>0.05). The MMSE scores of the patients in the observation group in 1 and 2 days after operation were significantly higher than those of the patients in the control group (P<0.05). There were no significant differences in the VAS score and in the Ramsay score of the patients at 4h after operation between the two groups (P>0.05).  The VAS score and the Ramsay score of the patients in the observation at 12h, 24h, and 48h after operation were significantly higher than those of the patients in the control group (P<0.05). The levels of the serum IgA, IgG, and IgM of the patients in both groups at 12h after operation were significantly lower than those before operation, and which of the patients in both groups at 24h after operation were significantly higher than those at 12h after operation, and which of the patients in the observation group at 12h and 24h after operation were significantly higher than those of the patients in the control group (all P<0.05). The levels of serum NPY, SP, and DA of the patients in both groups at 6h after operation were significantly higher than those at 6h before operation, but which of the patients in the observation group at 6h after operation were significantly lower than those of the patients in the control group (P<0.05). The total incidence (2.5%) of respiratory depression, vomiting, and nausea of the patients in the observation group was significantly lower than that (17.5%) of the patients in the control group (P<0.05). Conclusion: The combined applications of sufentanil, butorphanol, and dexmedetomidine during laparoscopic total hysterectomy of the patients can effectively reduce their cognitive dysfunction degree, improve their sedative effect, reduce their postoperative pain, regulate their immune function, and decrease their side effect rate.