Objective: Prenatal depression (PND) negatively affects the health and well-being of both mother and child. The aim of this study was to identify the direct and indirect determinants of prenatal depression symptoms (PNDS) among Arab-Bedouin women in southern Israel. Design: Data collection was conducted in two women's health centers from October 2017 to February 2018. Setting: Participants were recruited during visits to women's health centers in southern Israel. Participants: We recruited 376 Arab-Bedouin women as part of a larger study of perinatal health and well-being. We recruited 376 Arab-Bedouin women as part of a larger study of perinatal health and well-being. All women were 18+ years of age and 26–38 weeks of gestational age. Measurements: PNDS were measured by an Arabic version of the Edinburgh Postnatal Depression Scale. We computed path analyses to identify direct and indirect determinants of PND and estimated the contribution of stressful life events and social support. Results: Positive direct associations emerged between stressful life events, history of depression and gestational age, and PNDS; direct inverse associations were found between social support, PND awareness, and education, and PNDS. History of depression was the single strongest direct predictor of PNDS yet when considering combined direct and indirect effects, the contribution of stressful life events is greater. Stressful life events (via history of depression and PND awareness) and education (via PND awareness) had both direct and indirect effects on PNDS. Age of the mother indirectly affects PNDS via education and PND awareness. Polygamy emerged as neither a direct nor indirect predictor of PNDS. Conclusions: PNDS in the underserved and understudied Bedouin women has serval direct and indirect predictors. Interventions aiming at reducing stress and increasing social support, via PND awareness might be successful in reducing PND and possibly future postpartum depression.