Abstract: Objective To explore the analgesic effect of ketamine on postpartum cesarean section, postpartum depression and antidepressant mechanism. Methods A total of 360 patients with cesarean section were randomly divided into a control group, a low-dose ketamine group (low-dose group) and a high-dose ketamine group (high-dose group), with 120 cases in each group patients in the three groups were given automatic intravenous analgesia pump after operation. The dosage of ketamine in the pump was 0 mg/kg in the control group, 0.2 mg/kg in the low-dose group and 0.8 mg/kg in the high-dose group. Ramsay Sedation score and Visual Analogue Score (VAS) were used to evaluate the degree of sedation and pain at 5 time points of 4 h (T₁), 8 h (T₂), 12 h (T₃), 24 h (T₄) and 48 h (T₅) postoperatively. The effective pressing times and adverse reactions were recorded. According to the Edinburgh Postpartum Depression Scale (EPDS), the scores of EPDS at 1 week and 6 weeks after operation were evaluated. Serum leptin, noradrenaline (NE) and epinephrine(E) levels were measured before and 24 h after the use of the analgesic pump. Results The VAS scores of the low-dose group and the high-dose group at T₂, T₃, T₄ and T₅ were lower than those of the control group, and the score of the high-dose group was 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). The effective pressing times of analgesic pump in the low-dose and high-dose groups were less than those in the control group, and in high-dose group were less than those in low-dose group (P<0.05). There was no significant difference in adverse reactions among the three groups (P>0.05). The scores of EPDS in the high-dose group were lower than those in the control group and the low-dose group (P>0.05). There was no significant difference in the scores of EPDS among the three groups at 6 weeks after operation (P>0.05). There was no significant difference in serum leptin, NE and E levels among the three groups before and at 6 weeks after the use of analgesic pump (P>0.05). The serum leptin level increased and the serum NE and E levels decreased in the high-dose group at 24 h and 1 week after the use of analgesic pump, compared with the control group and the low-dose group (P<0.05). Conclusions Ketamine is safe for postoperative analgesia after cesarean section, and has antidepressant effect when the dosage reaches a certain level. Its antidepressant mechanism may be related to the regulation of serum leptin, NE and E levels.