Objective To evaluate the application of different doses of esketamine combined with propofol for oocyte retrieval during in vitro fertilization‑embryo implantation and select proper doses. Methods A total of 120 patients who underwent elective oocyte retrieval for in vitro fertilization‑embryo implantation were selected. According to the random number table method, they were divided into three groups (n=40): an esketamine 0.3 mg/kg group (group S1), an esketamine 0.4 mg/kg group (group S2), and an esketamine 0.5 mg/kg group (group S3). The three groups were intravenously administered with the corresponding doses of esketamine and propofol at 1.0‒1.5 mg/kg 1 min before surgery, in addition to the same other anesthetic dosage schemes. Their heart rate, mean arterial pressure (MAP) and saturation of peripheral oxygen (SpO2) were recorded before anesthesia (T0), 1 min after anesthesia induction (T1), 5 min after the beginning of oocyte retrieval (T2), at the time of awakening (T3), and 10 min after awakening (T4). Furthermore, the doses of propofol, the number of propofol doses administered, the postoperative recovery phrase, the Observer's Assessment Alert/Sedation (OAA/S) scores, and the Visual Analogue Scale (VAS) pain scores 5, 10, 30 min after awakening were recorded. Meanwhile, the incidences of adverse reactions, including hallucination, dizziness, respiratory depression, and nausea and vomiting within 30 min after awakening were recorded. Results Compared with those at T0, groups S1 and S2 showed decreases in heart rate and MAP at T1 ‒T3 (all P<0.05). Compared with group S3, group S1 presented reduced heart rate and MAP at T1‒T3 (all P<0.05), while group S2 showed reduced heart rate at T2 and decreased MAP at both T2 and T3 (all P<0.05). Compared with group S1, groups S2 and S3 presented decreases in the doses of propofol and number of propofol doses administered (all P<0.05), reduced postoperative recovery phrase (all P<0.05), and increases in OAA/S scores after awakening (all P<0.05). Compared with group S2, group S3 showed decreases in the doses of propofol and number of propofol doses administered (all P<0.05), reduced postoperative recovery phrase (P<0.05), and increases in OAA/S scores after awakening (P<0.05). Compared with group S1, the VAS pain scores after awakening decreased in groups S2 and S3 (all P<0.05). The incidences of respiratory depression in groups S1 and S2 were higher than that in group S3 (all P<0.05), and the incidence of respiratory depression in group S1 was higher than that in group S2 (P<0.05). There was no statistical difference in the incidences of hallucination, dizziness, nausea and vomiting among the three groups (all P>0.05). Conclusions In patients undergoing painless oocyte retrieval, a single intravenous dose of esketamine at 0.5 mg/kg is safe and effective, which can reduce the doses of propofol, and maintain stable intraoperative respiratory circulation, with a short postoperative recovery phrase and few adverse reactions.