BACKGROUND: Self-care behaviors during pregnancy significantly impacts mother and children's health. This study aimed to explore the self-care behaviors and the associations of these behaviors with the psychological well-being of women during pregnancy, as well as the mediating effects of different social support with these associations. METHODS: A cross-sectional data of 562 pregnant women at Hanoi Obstetrics & Gynecology Hospital and Ca Mau Obstetrics & Pediatrics in Vietnam were analyzed. Questions about self-care behaviors, pregnancy characteristics, social support, and psychological well-being were asked. Multivariate regression models were performed. Structural Equation Modeling (SEM) was employed to test the mediating effects of different social support with the association between self-care behaviors and psychological well-being. FINDINGS: Only 13% of pregnant women often or always did physical exercise at least three times a week, and 40% consumed enough fiber and five servings of vegetables a day. Only 78.7% always avoided alcohol drinking, and 53.9% of pregnant women avoided being exposed to second-hand smoking and 71,7% avoided using traditional medicine without physicians' prescriptions. Around 66% of pregnant women always or often had prenatal care checkups as scheduled. Information sources, social support and childbirth expectation were major drivers for self-care practices. SEM model showed that social support mediated the relationship between maternal health behaviors and mental well-being. CONCLUSION: This study highlighted the remarkable gaps in self-care practices among our pregnant women, which were significantly associated with their mental well-being. Social support-oriented consultancy and interventions should be warranted for improving behaviors and the mental well-being of pregnant women in Vietnam.