ObjectiveThis study aimed to identify the prevalence of postpartum depression (PPD) and the factors associated with PPD in Kampong Chhnang Province, Cambodia. Study designA cross-sectional study. ParticipantsThis study included 440 Cambodian women at 6–8 weeks postpartum who visited health centers between July and September 2021. Materials and methodsData were collected through face-to-face interviews by midwives and nurses using a structured questionnaire. The Edinburgh Postnatal Depression Scale (EPDS) in the Khmer language was used to screen for PPD, and suspected PPD was defined as a total EPDS score ≥ 10. Logistic regression analyses were performed to identify the factors associated with suspected PPD. FindingsThe average age of participants was 28.6 years old. The prevalence of suspected-PPD was 30.2 % (n = 133). Factors associated with suspected PPD were income dissatisfaction (adjusted odds ratio (AOR) = 2.66, 95 % confidence interval (CI) 1.27–5.56, P = 0.010), unintended pregnancy (AOR = 1.99, 95 % CI 1.10–3.61, P = 0.023), and a partner employed as a manual laborer (AOR = 3.85, 95 % CI 1.11–13.33, P = 0.034), farmer (AOR = 3.69, 95 % CI 1.11–12.31, P = 0.034), and factory worker (AOR = 5.43, 95 % CI 1.38–21.41, P = 0.016). In addition, poor relationship with partners (AOR = 2.14, 95 % CI 1.17–3.94, P = 0.014), poor relationship with mother-in-law (AOR = 3.51, 95 % CI 1.70–7.21, P < 0.001), and a history of depression before pregnancy (AOR = 6.34, 95 % CI 1.59–25.34, P = 0.009) were significantly associated with suspected-PPD. Key conclusions and implications for practiceThis study highlighted the need for mental health services in primary healthcare settings. Mental health training for healthcare workers, particularly primary-level nurses, should be prioritized and strengthened. Further clinical study on EPDS validation should be carried out to justify the appropriate cut-off EPDS score for Cambodian women. The EPDS should be integrated into routine PNC services to identify women with suspected-PPD. Education on PPD should be provided not only to the nurses and midwives, but also to the women and their families to support the mental health of pregnant and postpartum women.