Objective To investigate the effect of postoperative sleep disturbance by infusion of low dose esketamine during ambulatory laparoscopic cholecystectomy. Methods Patients undergoing ambulatory laparoscopic cholecystectomy under general anesthesia in General Hospital of Northern Theater Command between August and November 2024 were selected. They were randomly divided into esketamine group and control group based on a random number generator. Patients in the esketamine group received a continuous infusion of esketamine [0.3 mg/(kg·h)] during the operation. Patients in the control group received the equivalent volume of saline. The scores of the Athens Insomnia Scale on the first day before surgery, the first day after surgery, and the third day after surgery, the incidence of sleep disturbance and the Hospital Anxiety and Depression Scale score on the first day and the third day after surgery, mean artial pressure and heart rate during surgery, operation time, anesthesia time, recovery time, total dosage of remifetanil and vasoactive drug, postoperative adverse reactions, and the Visual Analogue Scale score on the day of surgery and the first day after surgery were compared between the two groups. Results A total of 105 patients were included, including 52 in the control group and 53 in the esketamine group. The differences were statistically significant in the incidence of sleep disorders on the first day after surgery (22.64% vs. 46.15%; χ2=6.440, P=0.011), the Athens Insomnia Scale score on the first day after surgery [4 (1.5, 5) vs. 5 (4, 7); Z=−2.933, P=0.003] , the cumulative amount of remifentanil used during surgery [884 (600, 1 112) vs. 572 (476, 872) μg; Z=−2.774, P=0.006], and the Visual Analogue Scale score on the day of surgery [2 (2, 3) vs. 3 (2, 3); Z=−2.488, P=0.013] between the esketamine group and the control group. There was no significant difference in mean arterial pressure, heart rate, operation time, anesthesia time, recovery time, vasoactive drug dosage, Hospital Anxiety and Depression Scale score or incidence of postoperative adverse reactions between the two groups (P＞0.05). Conclusion Continuous intraoperative infusion of low dose esketamine can improve postoperative sleep disturbance, without increasing the incidence of postoperative adverse reactions in patients undergoing ambulatory laparoscopic cholecystectomy.