Objective To observe and compare of the effects of esketamine and sufentanil induction for general anesthesia on postoperative analgesia in obese patients undergoing laparoscopic sleeve gastrectomy. Methods Patients scheduled for elective laparoscopic sleeve gastrectomy between March 2023 and March 2024， irrespective of gender， aged between 20 and 50 years， with a BMI ranging from 30.0 to 50.0 kg/m² and ASA Ⅰ or Ⅱ classification， were randomly allocated into two groups： the esketamine group （Group E） and the sufentanil group （Group S）， each consisting of 32 cases. During anesthesia induction， Group E received a dose of esketamine at 0.5 mg/kg while Group S received sufentanil at a dosage of 0.5 μg/kg； the remaining protocol remained unchanged. Heart rate （HR）， mean arterial pressure （MAP）， and SpO₂ were recorded at various time points： upon arrival （T0）， prior to anesthesia induction （T1）， immediately after induction （T2）， during intubation （T3）， at the conclusion of anesthesia administration（T4）， and during extubation（T5）. Postoperative pain scores using the Numeric Rating Scale（NRS） were assessed at specific intervals following surgery： one hour post?surgery（P0）， six hours post?surgery（P1）， twelve hours post?surgery（P2）， twenty?four hours post?surgery（P3）and forty?eight hours post?surgery（P4）. Additionally， intraoperative remifentanil consumption as well as the number of presses on the analgesic pump within forty?eight hours after surgery in both patient groups were documented along with any occurrences of adverse reactions. Results During the surgery， there was no statistically significant difference in mean arterial pressure （MAP） and heart rate （HR） between the two patient groups at T0 ~ T5 （P > 0.05）. At T2， both groups exhibited lower MAP and HR compared to T0； specifically， group S had a MAP of （91.81±8.94） mmHg and HR of （81.75 ± 13.37） beats/min， while group E had a MAP of （93.69 ± 9.96） mmHg and HR of （80.38 ± 13.2） beats/min， with group E showing values closer to baseline levels. At T3， both groups experienced a transient increase in MAP and HR （P < 0.05）； specifically， group S had a MAP of （97.56 ± 8.96） mmHg and HR of （86.47 ± 13.84） beats/min， while group E had a MAP of （101.03 ± 8.29） mmHg and （89.41 ± 15.32） times/min， with S group closer to baseline values. There was no statistically significant difference in the amount of remifentanil used during surgery between group S and group E （P > 0.05）， which were （2 071.88 ± 717.63） μg and （2 093.75 ± 718.39） μg， respectively. Compared with the postoperative conditions of the two groups， the NRS scores of group E （0.41 ± 0.61 ± 1.870.75， 2.47 ± 0.62） at P0， P1 and P2 were lower than those in group S （0.88 ± 0.71， 2.47 ± 0.72， 2.97 ± 0.54）， and the difference was statistically significant （P < 0.05）. The number of intravenous analgesia pump presses was significantly reduced in group E after surgery （P < 0.05）， with the postoperative analgesic pump compressions occurring 11.25±2.70 times in group S and 8.56 ± 2.23 times in group E. The incidence of postoperative nausea and vomiting （PONV） and hypotension in Group E （21.88%， 15.63%） was lower than that observed in group S （46.88%， 37.50%）， demonstrating statistical significance （P < 0.05）. Conclusion In comparison to sufentanil induction， the utilization of esketamine anesthesia induction is deemed safe for laparoscopic sleeve gastrectomy in obese patients， effectively mitigating postoperative acute pain and reducing the incidence of PONV.