Objective To explore the effect of esketamine on postoperative analgesia and postpartum depression on women undergoing caesarean section. Methods A total of 80 parturients with single and full‑term pregnancy who underwent the first cesarean section were selected. According to the random number table method, they were divided into two groups (n=40): a test group and a control group. Both groups underwent combined spinal epidural anesthesia (2 ml of 0.75% ropivacaine), followed by patient controlled intravenous analgesia (PCIA) after surgery. During PCIA, the control group was treated with 8 mg butorphanol diluted to 100 ml with normal saline, while the test group was treated with 100 mg esketamine+8 mg butorphanol diluted to 100 ml with normal saline. Then, the baseline data of the two groups were recorded. Their Ramsay sedation scores and Visual Analog Scale (VAS) scores were recorded immediately after operation (T0), at postoperative 4 h (T1), 8 h (T2), 12 h (T3), 24 h (T4), and 48 h (T5). The PCIA pressing times and total pressing times during the intervals of T0‒T1, T1‒T2, T2‒T3, T3‒T4 and T4‒T5, as well as adverse reactions were recorded. Furthermore, Edinburgh Postpartum Depression Scale (EPDS) and Hamilton Depression Scale (HAMD) were used to assess the postpartum depression of both groups one and six weeks after delivery. Results There was no statistical difference in Ramsay sedation scores between the two groups at each time point (P>0.05). The test group showed lower VAS scores than the control group at T1‒T5 (P<0.05). Both groups presented higher VAS scores at T1‒T5 than those at T0. The test group showed decreases in PCIA pressing times during the intervals of T0‒T1, T1‒T2, T2‒T3, and T3‒T4, compared with the control group (P<0.05). There was no statistical difference in PCIA pressing times between the two groups during T4‒T5 (P>0.05). There was no statistical difference in total pressing times between the two groups (P>0.05). There was no statistical difference in adverse reactions between the two groups (P>0.05). The incidence of postpartum depression in the test group was lower than that in the control group one week after delivery (P<0.05), and there was no statistical difference in the incidence of postpartum depression between the two groups six weeks after delivery (P>0.05). Conclusions The use of esmketamine in postoperative analgesia after cesarean section can not only produce good analgesic effect, but also reduce the incidence of early postpartum depression.