We investigated whether a formulation containing vitamins and minerals (vit&min) could improve the worsening of mood changes occurring after delivery ("a.d."). The study was performed in 552 healthy non-anaemic puerperal women ("p.w") without risk factors for puerperal depression ("p.d"). They were at their first full-term pregnancy, and spontaneously delivered healthy newborns. The Edinburgh Depression Postnatal scale (EPDS) evaluates the psychological status of "p.w". EPDS was administered the 3rd (visit 1), 15th (visit 2) and 30th (visit 3) day "a.d.". An EPDS >12 indicates a major susceptibility to "p.d". At the same time intervals, haemoglobin, iron and ferritin (haematological parameters) levels were evaluated. After visit 1, the subjects were randomized to vit&min treatment (group A; N.274) or to calcium/vitamin D3 treatment (group B; N.278). In both groups haematological parameters significantly increased without differences between the groups. EPDS score improved in both groups, but in the group A, the EPDS decrease was significantly larger (p < 0.05) in comparison to the group B. This effect is mainly evident in subjects with a basal EPDS ≥ 12. An early examination of psychological condition could select "p.w." with a high susceptibility to neuronal changes occurring postpartum. Vit&min favourably modulates brain functions antagonizing the evolution to "p.d".