Objective To explore the effects of dexmedetomidine (Dex) on cognitive function and HSP70 expression in mice models of sepsis, and to provide a basis for researches on brain protection in the setting of sepsis.Methods Eighty C57BL/6 mice were randomly divided into control group (CON group), Dex-only group (DEX group), sepsis group (LPS group), and Dex + sepsis group (D + L group), with 20 mice in each group. Firstly, DEX group and D + L group received 25 μg/kg of Dex via intraperitoneal injection, while CON group and LPS group were given the same volume of normal saline. Thirty minutes later, 5 mg/kg of lipopolysaccharide (LPS) was injected intraperitoneally in LPS group and D + L group to establish models of sepsis, while CON group and DEX group were given the same volume of normal saline. The Morris water maze was performed to assess the learning and memory of mice. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by ELISA, and levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in the hippocampus of mice were detected by chemical colorimetry. The hematoxylin-eosin (HE) staining was applied to observe the pathological changes in the hippocampal CA1 region, and the immunohistochemical assay and qPCR were used to determine the protein and mRNA expressions of heat shock protein 70 (HSP70) in the hippocampus.Results The escape latency of mice in each group on the 1st, 2nd, 3rd, 4th and 5th day were compared via repeated measures ANOVA, and the results revealed that the escape latency was significantly different among the time points (P < 0.05) and the groups (P < 0.05), and that the escape latency in the LPS group was longer than that in the CON group while that in the D + L group was shorter than that in the LPS group. Besides, the change trends of the escape latency were different among the groups (P <0.05). There was no statistically significant difference in swimming speed of mice among different groups (P >0.05). The time spent in the target quadrant in the LPS group was shorter than that in the CON group (P <0.05), and that in the D + L group was longer than that in the LPS group (P < 0.05). The number of platform crossings in the LPS group was lower than that in the CON group (P < 0.05), and that in the D + L group was higher than that in the LPS group (P < 0.05). The serum levels of TNF-α and IL-1β in the LPS group were higher than those in the CON group (P < 0.05), and those in the D + L group were lower than those in the LPS group (P < 0.05). Compared with the control group, levels of GSH and SOD were decreased (P <0.05), and the level of MDA was increased in the LPS group (P < 0.05). Compared with the LPS group, levels of GSH and SOD were increased (P < 0.05), and the level of MDA was decreased in the D + L group (P < 0.05). The positive expression rate of HSP70 protein in the LPS group was higher compared with that in the CON group (P < 0.05), while that in the D + L group was higher compared with that in the LPS group (P < 0.05). There was no statistically significant difference in the positive expression rate of HSP70 protein between the DEX group and the CON group (P > 0.05). The relative mRNA expression of HSP70 in the LSP group was higher than that in the CON group (P <0.05), while that in the D + L group was even higher compared with that in the LPS group (P < 0.05). There was no statistically significant difference in the relative mRNA expression of HSP70 between the DEX group and the CON group (P >0.05).Conclusions Dex can reduce inflammation and oxidative stress in mice models of sepsis, and improve the cognitive function of the mice. The underlying mechanism may be related to the upregulation of HSP70 expression.