Hippocampal pathology results were examined via hematoxylin-eosin staining; the concentrations of key inflammatory cytokines, namely interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-<i>α</i> (TNF-α), were determined by enzyme-linked immunosorbent assay; the protein expression was analyzed using Western blotting and immunofluorescence analysis.<h4>Results</h4>Esketamine administration post surgery significantly ameliorated cognitive deficits aggravated by preoperative acute sleep deprivation in aged mice. Here, IL6 is linked to Cognitive impairment.