Objective To investigate the effect of dexmedetomidine combined with sevoflurane on cognitive function and serum norepinephrine (NE), epinephrine (E) and cortisol (Cor) levels in patients after knee arthroscopy. Methods According to the random number table method, 200 patients who underwent knee arthroscopic surgery admitted to Guangxi International Zhuang Medical Hospital from March 2020 to February 2021 were divided into the control group (100 cases) and the experimental group (100 cases). Patients in the control group were anesthetised with normal saline combined with sevoflurane, and patients in the experimental group were anesthetised with dexmedetomidine combined with sevoflurane, patients in the two groups were observed for 12 h after surgery. The anesthesia-related indicators of patients in the two groups were compared, the cognitive function scores before and 1, 6 and 12 h after anesthesia , the stress response indicators before and 12 h after the surgery, and the occurrence of complications after anesthesia. Results The time of eye opening, time of spontaneous breathing and time of residence in resuscitation room in the experimental group were significantly shorter than those in the control group after anesthesia; compared with before anesthesia, the scores of the Mini Mental State Examination Scale (MMSE) of patients in the two groups at 1~12 h after anesthesia decreased first and then increased, and the experimental group was significantly higher than the control group at the different time points; compared with before surgery, the serum NE, E, and Cor levels of patients in the two groups increased significantly at 12 h after surgery, but the experimental group was significantly lower than the control group (all P <0.05); after anesthesia, the total incidence of complications between the two groups was compared, and the difference was not statistically significant (P >0.05). Conclusion Dexmedetomidine combined with sevoflurane can effectively reduce the stress response of patients after knee arthroscopy, improve postoperative cognitive function, the anesthetic effect and safety are good.