Objective To evaluate the effect of saliroside on perioperative neurocognitive disorder (PND) in sleep‑deprived aged mice. Methods A total of 48 healthy clean C57BL/6 mice, aged 18 months, weighing 30‒35 g, were selected. They were divided into three groups (n=16), according to the random number table method: a control group (group C), a sleep deprivation group (group D) and a sleep deprivation and salidroside group (group S). A mouse model of sleep deprivation was established through the modified multiple platform method using mice in group D and group S. Those in group S were intraperitoneally injected with 50 mg/kg salidroside for consecutive three days during sleep deprivation. Then, splenectomy was performed in the three groups. Morris water maze test was performed on days 1 and 3 after operation. Then, the escape latency and the number of crossing the platform were recorded. Then, the mice were sacrificed and their hippocampus were collected to determine the contents of interleukin‑6 (IL‑6), interleukin‑1β (IL‑1β) and tumor necrosis factor‑α (TNF‑α) by enzyme‑linked immunosorbent assay (ELISA). Results Compared with group C, groups D and S presented prolonged escape latency (P<0.05), a decreased number of crossing the platforms (P<0.05), and increased levels of IL‑6, IL‑1β and TNF‑α in the hippocampus on days 1 and 3 after operation (P<0.05). Compared with group D, group S showed shortened escape latency (P<0.05), an increased number of crossing the platforms (P<0.05), and decreased levels of IL‑6, IL‑1β and TNF‑α in the hippocampus on days 1 and 3 after operation (P<0.05). Conclusion Salidroside can relieve the effect of sleep deprivation on PND in aged mice, which may be associated with inhibiting hippocampal inflammation responses.