【Abstract】 Objective To observe the effect of sevoflurane and desflurane on short‑term olfactory memory in patients after laparoscopic surgery and to explore its mechanism. Methods A total of 76 patients, American Society of Anesthesiologists (ASA) Ⅰ or Ⅱ, aged 18‒60 years old, who were scheduled for laparoscopic surgery in the Second People's Hospital of Guiyang were enrolled. According to the random number table method, the patients were divided into two groups (n=38): a sevoflurane group (group S) and a desflurane group (group D). During the operation, they individually inhaled with 1.0 minimum alveolar concentration (MAC) sevoflurane or desfluran to maintain anesthesia, other drugs were the same. At 30 min before anesthesia (T1) and when Aldrete Recovery Score≥9 in the post‑anesthesia care unit (PACU) (T2) respectively, heart rate and mean arterial pressure (MAP) of the two groups were recorded； the olfactory memory was evaluated by the Connecticut Chemosensory Clinical Research Center olfactory test, and the score of olfactory recognition was recorded; the levels of plasma S100β protein, neuron specific enolase (NSE), and melatonin were determined using enzyme‑linked immunosorbent assay (ELISA). Results There was no statistical difference in heart rate and MAP at T1 and T2 between group D and group S (P>0.05). At T1, there were no significant differences in the score of olfactory recognition, the levels of S100β protein, NSE and melatonin between the two groups (P>0.05). At T2, the score of olfactory recognition and melatonin in group S were lower than those in group D (P<0.05), and the levels of S100β protein and NSE in group S were higher than those in group D (P<0.05). Compared with T1, at T2, the score of olfactory recognition and melatonin in group S were decreased (P<0.05), and the levels of S100β protein and NSE were increased (P<0.05); there was no significant difference in the indexes of group D (P>0.05). Conclusions Desflurane cannot affect the short‑term postoperative olfactory memory of patients undergoing laparoscopic surgery, while sevoflurane affects the postoperative short‑term olfactory memory of patients, which is may be related to the increases in plasma S100β protein and NSE concentration and reduction of melatonin levels.