Purpose <p>Psychological factors, such as anxiety, depression, and catastrophizing, may increase the risk of chronic postsurgical pain (CPSP) following Cesarean delivery (CD). We sought to evaluate whether postpartum depression (PPD) after CD is associated with CPSP and assess the potential mediating effect of PPD on the relationship between acute severe postoperative pain and CPSP.</p> Methods <p>We conducted a secondary analysis of a previous randomized trial. In the original trial, 290 patients undergoing CD in Nepal were randomized to receive either 100&#xa0;µg of intrathecal morphine or normal saline in addition to their spinal anesthesia with the goal to investigate the relationship between intrathecal morphine use and CPSP development. Eight weeks after CD, we used the Edinburgh Postnatal Depression Scale to identify patients with a provisional diagnosis of PPD (scores ≥ 12). The study outcomes were the occurrence of CPSP at three and six months.</p> Results <p>Out of 276 patients analyzed, 20 (7%) experienced PPD. The incidences of CPSP at three and six months were 18% (52/276) and 15% (42/276), respectively. A multivariable model revealed that the odds of experiencing CPSP at three months postpartum were significantly higher in patients with depression (odds ratio [OR], 4.24; 95% confidence interval [CI], 1.53 to 11.7; <i>P</i> = 0.005) than in those without depression. Similarly, PPD was independently associated with an increased incidence of CPSP at six months post CD (OR, 4.05; 95% CI, 1.42 to 11.5; <i>P</i> = 0.009). Causal mediation analysis showed no mediating effect of PPD between acute severe postoperative pain and CPSP.</p> Conclusions <p>In this secondary analysis of a previous randomized trial, we found a significant association between PPD and CPSP following CD.</p>