Aims: Postoperative cognitive dysfunction (POCD) is a common complication associated with poor outcome. Our previous study has shown that living with familiar observers in the same cage reduces anxiety of mice with surgery. Anxiety can impair learning and memory. Thus, this study was designed to determine whether living with familiar observers attenuated the dysfunction of learning and memory of mice with surgery. Methods: Six- to eight-week-old CD-1 male mice or 18-month-old C57BL/6 male mice had left carotid artery exposure under isoflurane anesthesia. They lived with non-surgery male mice at 2 (number of surgery mice) to 3 (number of non-surgery mice) ratio or with other surgery mice. Mice were subjected to light and dark box test 3 days after surgery to measure their anxiety levels and novel object recognition and fear conditioning tests from 5 days after surgery to measure their learning and memory. Blood and brain were harvested for biochemical analysis. Results:Living with familiar observers that lived with surgery mice for at least 2 weeks before the surgery and then after surgery reduced the anxiety and dysfunction of learning and memory in young adult male mice. Living with unfamiliar observers that lived with surgery mice after the surgery but not before the surgery did not have those effects on the mice with surgery. Living with familiar observers attenuated learning and memory dysfunction after surgery also in old male mice. Living with familiar observers attenuated inflammatory response in the blood and brain and the activation of the lateral habenula (LHb)-ventral tegmental area (VTA) neural circuitry, which has been shown to be important for POCD. Wound infiltration with bupivacaine attenuated the activation of LHb-VTA. Conclusion: These results suggest that living with familiar observers attenuates POCD and neuroinflammation, possibly via inhibiting the activation of the LHb-VTA neural circuitry.