Objective To compare the pathological changes of POCD induced by ketamine and sevoflurane in aged mice，and explore its possible mechanism. Methods 12-month-old C57BL/6 mice were randomly divided into Control group，Ketamine group and Sevoflurane group. The mice were anesthetized with a total dose of 200 mg/kg of ketamine and 3% sevoflurane for 6 hours. Morris water maze was used to test the learning and memory ability. Then，excitatory postsynaptic potential was detected by long-term potential test，synaptic state was detected by Golgi staining，Aβ deposition in brain was observed by immunohistochemical staining，and the expression of NMDAR and apoptosis protein in brain were detected by Western blot. Results Compared with Control group，no matter ketamine or sevoflurane caused significant increases of escape latency，a decrease of platform crossing number，and an increase of resident time in the first quadrant at the same swimming speed. However，all indexes of Morris water maze mice in Ketamine group were better than those in Sevoflurane group. In addition，both ketamine and sevoflurane caused LTP inhibition in mice，reduced the density and length of dendritic spines in synapses，and increased Aβ deposition. However，compared with Ketamine group，mice in Sevoflurane group had lower LTP intensity，decreased dendritic spines density，and increased Aβ deposition. In addition，Western blot showed that both ketamine and sevoflurane significantly inhibited the expression of NMDAR，and the Caspase-3 signaling pathway was significantly activated. The inhibition of ketamine on NMDAR was better than sevoflurane，and the expression of bcl-2 was higher in mice of Ketamine group than Sevoflurane group. Conclusion Compared with Sevoflurane group，Ketamine has less effects on cognitive function in aged mice，which involving the inhibition of NMDAR receptors，mediates the decrease of Aβ deposition and the increase of LTP level.