Introduction: Postpartum depression has a prevalence range from 6.5% to 12.9%. The NT-3 gene is involved in alterations in patients with mood disorders. Purpose: The aim was to describe a possible correlation between the NT-3 expression and the Edinburgh Postnatal Depression Scale (EPDS). Material and Methods: It was a clinical, comparative, prospective, and cross-sectional study. Puerperal women were asked to answer the EPDS while mRNA was extracted from peripheral blood and through the qPCR the relative expression of NT-3 was determined using the delta-delta-(CT) method (2-DDCT). Results and Discussion: The NT-3 expression was quantified in 5 patients with depression and 6 healthy women. A fold change of 1.7 was obtained when the NT-3 is present in the group with depression in relation to the control group. Also, a positive significant correlation was found between the gene relative expression and the EPDS score (r2 = 0.60516, p = 0.04853). The fold change when the NT-3 is expressed means a risk to develop puerperal depression in our population, which is visualized as an inevitable disease for a wide range of patients. Conclusion: It was concluded that the NT-3 gene is effectively correlated with the EPDS score and explains, in part, a subgroup of patients that will develop this health complication.This work was partially supported by ASCILA (fellowship for VVJ). Financial support (Master Degree scholarship for AGS) of CONACYT is also gratefully acknowledged.