Objective: To explore the influences of esketamine combined with ropivacaine for femoral nerve block on analgesic effect and cognitive function after knee arthroplasty. Methods: A total of 80 patients undergoing knee arthroplasty were enrolled between August 2024 and August 2025.They were divided into observation group and control group. The control group was given ropivacaine, while observation group was given esketamine combined with ropivacaine for femoral nerve block. The postoperative duration of sensory and motor block, scores of visual analogue scale (VAS) under resting and motion states at 2h, 8h and 24h after surgery, scores of Montreal Cognitive Assessment (MOCA) and the incidence of adverse reactions were compared. Results: After surgery, the duration of sensory and motor block in observation group was longer than that in control group (P<0.05). At 2h, 8h and 24h after surgery,VAS scores under resting and motion states in observation group were significantly lower than those in control group (P<0.05). At 1d and 3d after surgery, MoCA scores in observation group were higher than those in control group (P<0.05), but there was no significant difference in MoCA score between the two control groups at 7d after surgery (P>0.05). During operation and hospitalization, There was no significant difference in the probability of joint stiffness, vascular injury, deep vein thrombosis and wound infection between the two groups (P>0.05). Conclusion: The application of esketamine combined with ropivacaine for femoral nerve block in knee arthroplasty can effectively prolong the duration of sensory and motor block, and relieve pain, which is beneficial to preserve postoperative cognitive function, with good safety.