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OBJECTIVE: To investigate the effects of parecoxib on postoperative cognitive dysfunction, and serum levels of neuron-specific enolase (NSE) and S100β protein (S100β) in elderly patients undergoing surgery. PATIENTS AND METHODS: The retrospective cohort study method was used to collect the clinical data of 94 elderly patients who underwent elective orthopedic and general anesthesia surgery in our hospital from September 2020 to February 2022. 94 patients were divided into the control group (47 cases) and the study group (47 cases), according to different intervention methods. In the study group, 40 mg of parecoxib was injected intravenously into patients 30 min before the induction of anesthesia, and the patients in the control group were given the same dose of normal saline intravenously before the operation. The basic clinical data of the patients were collected. The levels of the indexes before operation and 6 hours after operation were compared between the two groups, including the Montreal Cognitive Scale (MoCA) score, inflammatory factor indicators [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), interleukin-1β (IL-1β), monocyte chemokine-1 (MCP-1), and inducible nitric oxide synthase (iNOS)], serum cortisol (CORT), beta-amyloid (β-AP), adiponectin (ADP), NSE, and S100β. RESULTS: No significant differences in the preoperative MoCA score, TNF-α, IL-6, CRP, IL-10, IL-1β, MCP-1, iNOS, CORT, β-AP, ADP, NSE, and S100β levels were observed between the two groups (p>0.05). The postoperative MoCA score in the study group was significantly higher than that in the control group (p<0.05). The postoperative levels of TNF-α, IL-6, CRP and IL-1β in the study group were significantly lower than those in the control group (p<0.05), and the postoperative levels of IL-10, MCP-1 and iNOS in the study group were significantly higher than those in the control group (p<0.05). CONCLUSIONS: Parecoxib can notably inhibit the levels of postoperative inflammatory cytokines, improve neurological dysfunction, and reduce the occurrence of postoperative cognitive dysfunction in patients. The contents of serum NSE and S100β have potential value in the diagnosis of postoperative cognitive dysfunction in elderly patients. [ABSTRACT FROM AUTHOR]