Objective To observe the effect of A1 astrocytes on cognitive impairment in infancy mice after single‑time anesthesia and surgery. Methods A total of eight healthy C57BL/6 pregnant mice of SPF grade were gestated for 18 d. The 8‑day‑old infancy mice were randomly divided into two groups (n=27), according to the random number table method: a control group and a single‑time anesthesia and surgery group. The infant mice of control group were given 40% oxygen, while the single‑time anesthesia and surgery group were given 40% oxygen and 3% sevoflurane anesthesia. After anesthesia, the infant mice of single‑time anesthesia and surgery group underwent an exploratory surgery. Three infant mice in each group were killed after anesthesia 1.5 h after establishing the single‑time anesthesia and surgery model. Brain tissue was taken for frozen sections, and the expression of glial fibrillary acidic protein (GFAP) and complement C3 (C3) in the hippocampus was detected using immunofluorescence staining; at 30 d of age, 6 mice in each group were sacrificed after anesthesia to the hippocampus, and the content level of postsynaptic density protein (PSD) 95 was detected by Western blot. The remaining 18 infant mice were subjected to Morris water maze experiments at the age of 30−36 d, recording the escape latency and the platform crossing times. Results Compared to mice in the control group, the escape latency of mice in the Morris water maze navigation experiment was significantly prolonged (all P<0.05) in the anesthesia surgery group on the day 6 and 7, and the number of platform crossings in the Morris water maze spatial exploration experiment was significantly reduced (P<0.05) on the day 7. Compared to the mice in control group, the C3/GFAP levels of mice in the hippocampal region were significantly increased in the anesthesia surgery group, indicating that the hippocampal region astrocytes were more polarized towards type A1 (P<0.05), and the PSD95 expression level was significantly reduced (P<0.05). Conclusions Single anesthesia surgery in infant mice can cause cognitive function impairment. Excessive polarization of astrocytes to type A1 leads to a decrease in the PSD95 level in the hippocampal region.