The objectives of this cross-sectional study were to estimate the prevalence of depressive symptoms and affective disorders during pregnancy in a maternity hospital in Argentina and to explore potential risk factors. Symptoms of depression were measured with the Edinburgh Postnatal Depression Scale (EPDS), and the Mini International Neuropsychiatric Interview (MINI) for diagnosis at mid-pregnancy. 50.7%, 95% CI: 43.7; 57.8 screened positive using a score ≥ 10 and 23% of pregnant women were diagnosed with affective disorders, 11% unipolar, and 12% bipolar. Personal and family depression history were main risk factors. It is advised to routinely screen for depression during pregnancy.