Objective To compare the postoperative cognitive function of patients undergoing general anesthesia using three strategies:sevoflurane alone, sevoflurane plus propofol, and sevoflurane plus dexmedetomidine. Methods Ninety patients aged 18 to 65 years who were scheduled to undergo laparoscopic hysteromyomectomy were selected for this study. The American Society of Anesthesiologists (ASA) was classified as Grade Ⅰ or Grade Ⅱ. Ninety patients were divided into three groups by random number table:sevoflurane group, sevoflurane-propofol group and sevoflurane-dexmedetomidine group, with 30 patients in each group. The induction drugs of anesthesia were the same in the three groups. Sevoflurane group was maintained with 1-1.2 minimum alveolar concentration (MAC) sevoflurane; sevoflurane-propofol group was maintained with 0.5 MAC sevoflurane and target controlled infusion propofol (target blood concentration was 2-3 μg/mL); and sevoflurane-dexmedetomidine group was maintained with 0.5 MAC sevoflurane, intravenous pump loading dose of dexmedetomidine was 1 μg/kg (pump infusion for 10 min), and dexmedetomidine was continuously pumped at a dose of 0.2 μg/(kg·h) until 30 min before the end of the operation. Cognitive function was measured 1 d before operation and 7 d after operation, and plasma levels of inflammatory factors were measured before operation and 24 h after operation. Results There were no significant differences in age, body mass index, preoperative score of mini-mental state examination scale, operation time or blood loss among the three groups (all P>0.05). The Hopkins visual learning test (HVLT1) and forward digit span test (FSDT) scores 7 d after operation (23.22±4.75, 2.39±0.69) were significantly higher in the sevoflurane-dexmedetomidine group than those in the sevoflurane group (21.00±4.96, 2.17±0.39), but lower than those in the sevoflurane-propofol group (24.89±6.20, 2.84±0.96), and the differences were statistically significant (all P<0.05). The plasma interleukin 6 (IL-6) level ([19.93±10.04] pg/mL) in the sevoflurane-dexmedetomidine group was significantly lower than those in the sevoflurane group ([36.06±17.03] pg/mL, P<0.05) and sevoflurane-propofol group ([39.99±19.39] pg/mL, P<0.05). Conclusion Compared with sevoflurane alone and sevoflurane plus propofol, patients with sevoflurane plus dexmedetomidine for general anesthesia have better postoperative cognitive function, which may be related to the low level of IL-6 after surgery.