Abstract: Object To explore the analgesic effect of ketamine on postpartum cesarean section, postpartum depression and antidepressant mechanism. Method The total of 360 patients with cesarean section, ASAI or II, were randomly divided into the control group, the low-dose group and the experimental group, with 120 cases in each group. Three groups of patients were given a self-controlled intravenous analgesia pump. The doses of ketamine in the analgesic pump were: 0 mg/kg in the control group, 0.2 mg/kg in the low-dose group, and 0.8 mg/kg in the experimental group. Then, the Ramsay sedation score and visual analogue scale (VAS) were used to evaluate the degree of sedation and pain at 4 hours (T1), 8h (T2), 12h (T3), 24h (T4), and 48h (T5). Record the number of effective presses and adverse reactions of analgesia pump after operation. Evaluation of EPDS scores at 1 week and 6 weeks after surgery according to the Edinburgh Postnatal Depression Scale (EPDS). Serum leptin, NE and E levels were measured before and after 24 hours of use of the analgesic pump. Result The VAS scores of the low dose group and the experimental group at T2, T3, T4 and T5 were significantly lower than those of the control group, and the score of the experimental group was significantly lower than that of the low dose group (P<0.05). There were no significant differences of the Ramsay scores between the three groups (P>0.05). Compared with the control group the analge pump effective compression times of low dose group and experimental group within the T0-T4 time period were significantly less than control group. The experimental group was significantly less than the low dose group (P<0.05). There was no significant difference in the incidence of adverse reactions between the three groups (P>0.05). The EPDS score of the experimental group was significantly lower than that of the control group and the low dose group (P<0.05). There were no significant differences in EPDS scores between the three groups (P>0.05). There was no significant difference in serum leptin, NE and E levels between the first three groups using analgesia pump. After 24 hours of analgesia pump, serum leptin levels were elevated in the experimental group, serum NE and E levels were decreased, and the difference was statistically significant compared with the control group and the low dose group (P<0.05). Conclusion Ketamine has effect after cesarean section, and it has high safety. The dose reaches a certain level to exert antidepressant effect. The antidepressant mechanism may be related to the regulation of serum leptin, NE and E levels.