The use of intravenous dexmedetomidine during surgery has been shown to suppress inflammatory cytokines peri-operatively. It has also been demonstrated that dexmedetomidine may benefit cognitive function in elderly patients following surgery; however, it is not clear whether dexmedetomidine reduces postoperative cognitive dysfunction (POCD) via the suppression of inflammatory cytokines. The aim of the present study was to investigate the effects of dexmedetomidine on early POCD and inflammatory cytokines in elderly patients undergoing laparoscopic cholecystectomy (LC). The study comprised 120 elderly patients undergoing selective LC, who were randomly allocated to receive either dexmedetomidine intravenously (DEX group, n=60) or the same volume of normal saline (control group, n=60). Cognitive function was assessed by Mini-Mental State Examination (MMSE) scores 1 day prior to surgery, 6 h following surgery and postoperatively on days 1 and 2. Interleukin (IL)-1β, IL-6 and C-reactive protein (CRP) levels were also measured at these time-points. On the basis of whether the patients had POCD on the first day after surgery, patients were divided into a POCD group and a non-POCD group. Blood cytokine levels were compared between the patients with and without POCD. A total of 100 patients completed both pre- and postoperative MMSE tests. At 1 day following surgery, POCD occurred in 10/50 (20%) patients in the DEX group and in 21/50 (42%) patients in the control group (P=0.017). At 6 h following surgery, IL-1β, IL-6 and CRP levels showed significant increases (P<0.01) compared with the baseline levels in the two groups. Furthermore, in the control group, CRP levels showed a significant increase on day 1 (P<0.001) and day 2 (P=0.017) postoperatively. In the DEX group compared with the control group, IL-1β, IL-6 and CRP levels were markedly decreased at 6 h and 1 day after surgery (P<0.01). Concentrations of IL-1β, IL-6 and CRP were significantly higher in patients who developed POCD on day 1 following surgery than in the patients who did not develop POCD (P<0.05). The findings of the current study support the hypothesis that dexmedetomidine administration during anesthesia decreases the incidence of early POCD, most likely by the mechanism of reduction of the inflammatory response level.