BackgroundAntenatal depression is a commonly seen mental health concern for women. This study introduced a multicenter cross-sectional survey with a large sample to provide new insights into pregnant women’s depression, its socio-demographic and obstetric characteristics correlates, and its perceived stress among Chinese pregnant women.MethodsThis study conducted an observational survey according to the STROBE checklist. The multicenter cross-sectional survey was performed from August 2020 to January 2021 by distributing paper questionnaires among pregnant women from five tertiary hospitals in South China. The questionnaire included socio-demographic and obstetrics information, the Edinburgh Postnatal Depression Scale, and the 10-item Perceived Stress Scale. For the analyses, the Chi-square test and Multivariate logistic regression were utilized.ResultsAmong 2014 pregnant women in their second/third trimester, the prevalence of antenatal depression was 36.3%. 34.4% of pregnant women reported AD in their second trimester of pregnancy, and 36.9% suffered from AD in third trimester of pregnancy. A multivariate logistic regression model indicated that unemployed women, lower levels of education, poor marital relationships, poor parents-in-law relationships, concerns about contracting COVID-19, and higher perceived stress could aggravate antenatal depression among participants (p<0.05).ConclusionThere is a high proportion of antenatal depression among pregnant women in South China, so integrating depression screening into antenatal care services is worthwhile. Maternal and child health care providers need to evaluate pregnancy-related risk factors (perceived stress), socio-demographic factors (educational and professional status), and interpersonal risk factors (marital relations and relationship with Parents-in-law). In future research, the study also emphasized the importance of providing action and practical support to reduce the experience of antenatal depression among disadvantaged sub-groups of pregnant women.