Objective  To explore the effects of sevoflurane anesthesia on spatial recognition and expressions of pCreb and early growth response factor 1 (Egr1) in hippocampus tissues of aged mice. Methods  A total of 12 Eighteen-month-old mice were randomly divided into the anesthesia group (n=6) and control group (n=6). Mice of the anesthesia group and control group inhaled 3% sevoflurane and 100% oxygen for 4 h, respectively. Spatial learning and memory abilities were tested by the Morris water maze 48 h after anesthesia. The spatial probe test was conducted 24 h after memory acquisition test. Hippocampus tissues were harvested 15 min after the spatial probe test and expressions of Egr1, Creb, and pCreb in hippocampus tissues were detected by Western blotting and RT-qPCR. Results  The escape latency of anesthesia group was significantly longer than that of the control group on day 4, 5, and 6 (P<0.05). The time spent in the target quadrant of the control group was significantly longer than that of the anesthesia group and the percentage of distance of the control group was significantly higher than that of the anesthesia group during the spatial probe test (P<0.01). Compared with the control group, the expression of Egr1 in hippocampus tissues of the anesthesia group remarkably decreased (P<0.05) and the expression of pCreb decreased (P<0.05). The difference of the expression of Creb between two groups was not significant (P>0.05). Conclusion  Sevoflurane down-regulates expressions of pCreb and Egr1 in hippocampus tissues and affects the spatial recognition of aged mice.