This study sought to determine whether intraoperative dexmedetomidine infusion might reduce the incidence of postoperative cognitive dysfunction (POCD) and alleviate the neuroinflammatory response in patients who have undergone arthroscopic shoulder surgery. A total of 80 patients over 60 years of age who had undergone arthroscopic shoulder surgery in the beach chair position were randomly allocated to either the dexmedetomidine group (Group D) or the control group (Group C). Dexmedetomidine (0.6 μg/kg/h) or a comparable amount of normal saline was infused into each group during the surgery. The early incidence of POCD was assessed by comparing cognitive tests on the day before and 1 d after surgery. The neuroinflammatory response with the S100 calcium-binding protein B (S100β) assay was compared prior to anesthetic induction and 1 h following surgery. The incidence of POCD was comparable between groups D (n = 9, 22.5%) and C (n = 9, 23.7%) (p = 0.901). However, the results of the cognitive test revealed a significant difference between the groups after surgery (p = 0.004). Although the S100β levels measured at the end of surgery were significantly higher than those at baseline in both groups (p < 0.001), there was no difference between the groups after the surgery (p = 0.236). Our results suggest that intraoperative dexmedetomidine infusion neither reduce the incidence of early POCD nor alleviated the neuroinflammatory response in patients undergoing arthroscopic shoulder surgery.