Background:Postoperative delirium (POD) is an acute brain dysfunction that mainly occurs in elderly patients after surgery. Postoperative pain is an important factor in the occurrence of POD, and effective pain management can reduce the risk of POD. Our study aims is to investigate the effect of ultrasound-guided femoral nerve block (FNB) on postoperative pain and the occurrence of POD after knee arthroplasty, and whether its mechanism is related to oxidative stress, inflammatory factors.Methods:Patients aged 65 to 80 years who were scheduled to undergo knee arthroplasty under general anesthesia from 2020 to 2023 were randomly divided into 2 groups: the control group (NC group) and the FNB analgesia group (FNB group). After anesthesia induction, the FNB group received ultrasound-guided FNB, whereas the NC group received an equal volume of normal saline. Visual analog scale (VAS), incidence of POD. the postoperative Quality of Recovery-15-Chinese version (QoR-15C) was been evaluated. Venous blood samples were collected from patients to detect the level of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and C-reactive protein (CRP).Results:The VAS scores in the FNB group were significantly lower than those in the NC group at 24h. The summation of perioperative remifentanil usage and the number of remedial analgesia in the FNB group were significantly lower than those in the NC group. The incidence rate of POD in the FNB group is lower than the NC group. The occurrence of POD was markedly lower in the FNB group compared to the NC group. Compared with the NC group, the levels of MDA, GSH-Px, and CRP in the FNB group were lower on the first and third days after surgery. The QoR-15C score in the FNB group was higher on the 5th day after surgery.Conclusion:Ultrasound-guided FNB can reduce the incidence of POD after knee replacement surgery, and its mechanism may be related to analgesia improvement and reduction of postoperative inflammatory reaction.