Objective To explore the application effect of Esketamine and Fentanyl on pain rating index and sleep quality in patients with phantom limb pain after traumatic amputation. Methods A total of 84 patients with phantom limb pain after traumatic amputation treated in the hospital between June 2019 and August 2020 were selected as the research subjects, and they were divided into the control group and the observation group by drawing lots, with 42 cases in each group.The control group was treated with Fentanyl, while the observation group was given Fentanyl+Esketamine.The pain rating index and sleep quality, etc.were compared between the two groups after medication. Results After treatment, the scores of pain rating index (PRI), visual analogue scale (VAS) and present pain intensity (PPI) in the observation group were lower than those in the control group, and the differences were statistically significant (P＜0.05).After treatment, the scores of sleep time, sleep efficiency, sleep disorder, hypnotic drugs and daytime function were lower in the observation group than those in the control group, and the differences were statistically significant (P＜0.05). Conclusion Esketamine combined with Fentanyl can effectively relieve the pain and enhance the sleep quality in patients with phantom limb pain after traumatic amputation.