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Background and Aims Central sensitization is a phenomenon whereby the central nervous system becomes hyperresponsive to nociceptive input, resulting in amplified pain signals and increased sensitivity to stimuli that would normally be less painful or non-painful. Central sensitization may underlie chronic postpartum pain, yet its risk factors remain poorly understood. We aimed to identify independent predictors of severe postpartum central sensitization at 6–10 weeks postpartum.Methods We performed a secondary analysis of data from a clinical trial investigating association between labor epidural analgesia and postpartum depression. After obtaining written informed consent, term pregnant participants completed validated pre-delivery questionnaires evaluating pain and psychological vulnerabilities. Data on labor pain intensity, obstetric interventions, and neonatal outcomes were systematically collected. An online survey was conducted at 6–10 weeks postpartum to assess severe central sensitization, defined as a Central Sensitization Inventory (CSI) score of ≥50.Results Of the 816 participants, 401 (49.1%) had severe central sensitization at 6–10 weeks postpartum. Multivariable analysis identified six independent predictors of severe central sensitization: Pre-delivery factors including higher Edinburgh Postnatal Depression Scale (EPDS) score (adjusted odds ratio (aOR) 1.09, 95% confidence interval (CI)1.03–1.14, p=0.0009); a higher pre-delivery CSI score (aOR 1.08, 95%CI 1.06–1.10, p<0.0001); a higher Angle Labor Pain Questionnaire (A-LPQ) Enormity of pain subscale score (aOR 1.01, 95%CI 1.00–1.03, p=0.011), and a higher Fear-Avoidance Components Scale (FACS) pain-related anxiety subscale score (aOR 1.03, 95%CI 1.01–1.05, p=0.015); and obstetric complications including manual removal of placenta (aOR 4.33, 95%CI 1.17–16.03, p=0.028) and intrauterine growth restriction (aOR 12.29, 95%CI 1.29–117.57, p=0.029) (Area under the curve (AUC): 0.79 (95%CI 0.76–0.82)).Conclusions Greater pre-delivery pain and psychological vulnerabilities, and obstetric complications were independently associated with the development of severe central sensitization at 6–10 weeks postpartum. Recognition of these risk factors may help identify women at risk and inform targeted strategies to mitigate persistent postpartum pain.