Objective To investigate the effect of intraoperative infusion of low‑dose ketamine (Ket) on postoperative fatigue (POF) in patients undergoing laparoscopic hysterectomy. Methods Ninety patients scheduled to gynecological laparoscopic hysterectomy were divided into two groups (n=45),according to the random number table method: Ket group (group K) and control group (group N). Patients in group K were given Ket 0.5 mg/kg after induction of anesthesia, then at an infusion rate of 0.25 mg·kg−1·h−1 until the end of surgery. Group N was given the same volume of saline solution with the same method. The occurrence of POF was evaluated by Fatigue Scale‑14 (FS‑14) score. The primary indexes were FS‑14 scores and the incidences of POF at 3, 7 and 30 d after surgery. The secondary indexes included intraoperative heart rate, mean arterial pressure (MAP), postoperative Visual Analogue Scale (VAS) scores, Ramsay scores after extubation, and adverse reactions such as nausea and vomiting. Results Compared with the group N, the incidence of POF and FS‑14 score in group K were significantly lower at 3 d after surgery (P<0.05). Compared with the group N, there was no significant difference in FS‑14 score and incidence of PDF at 7 d and 30 d after operation in group K (P<0.05). Ramsay scores after extubation in group K were also significantly higher than in group N (P<0.05). Patients in group K showed significantly lower VAS scores at 3 and 7 d after surgery (P<0.05). There was no significant difference in VAS scores between the two groups at 30 d after operation (P>0.05). There were no significant differences in adverse events such as intraoperative heart rate and MAP, nausea and vomiting between the two groups (P>0.05). Conclusions Intraoperative use of low‑dose ketamine can reduce the incidence of fatigue in patients undergoing gynecologic laparoscopic surgery at 3 d after surgery, with a good sedative and analgesic effect.