ABSTRACT Background: To investigate the effect of pre-emptive parecoxib sodium, given in addition to routine analgesic treatment, on post-operative cognitive function in elderly patients. Methods: Seventy elderly patients were included, who were 65-82 years of age, 48-75 kg of weight, and ASA grade I-II. Preoperative mini mental state examination (MMSE) score was ≥21 points. Patients were randomly divided into two groups: control group (group C) and parecoxib sodium group (group P). Before induction of general anesthesia, 40 mg of parecoxib sodium was injected intravenously in group P and the same volume of saline was injected in group C. Patient-controlled intravenous analgesia (PCIA) containing fentanyl and tramadol was used for post-operative pain control. A 3 ml blood sample was obtained from the peripheral vein one day before surgery, 1, 4, 24, and 72 h after surgery, and plasma cortisol, IL-6 and S100β concentrations were measured. Cognitive function was evaluated by measuring the MMSE score and a neurological test battery within 72 h after surgery. The occurrence of post-operative cognitive dysfunction (POCD), the dosage of fentanyl and tramadol used in PCIA, and the rate of additional fentanyl administration were recorded. Results: Compared to group C, post-operative plasma cortisol concentration decreased, the amount of fentanyl and tramadol used in PCIA was reduced, the rate of additional fentanyl administration decreased, and the rate of POCD was reduced in group P (P < 0.05). Conclusion: Pre-emptive analgesia with 40 mg of parecoxib sodium can reduce the incidence of POCD in elderly patients.