This study assessed the reliability, validity, sensitivity, specificity, and predictive values of the Spanish Postpartum Depression Screening Scale (PDSS–Spanish Version) for Mexican women. The scale was administered at 6 weeks (T1; n = 149) and between 4 and 6 months postpartum (T2; n = 156). Women also completed the Beck Depression Inventory–Second Edition (BDI-II) and the mood module of the Standardized Clinical Interview for DSM-IV (SCID). At both time points, the internal consistency value of the PDSS-Spanish Version was α = .96. Concurrent validity was adequate, compared with the BDI-II (T1: r = .75; T2: r = .74, ps < .01) and the SCID (T1: r = .43; T2: r = .36, ps < .01). Based on receiver operator characteristic curves, cutoff scores on the PDSS-Spanish Version of 60 for depressive symptoms (BDI-II as gold standard) and 80 for major depression (SCID) showed high sensitivity (>88.9%) but low specificity (60.9% to 70.6%). More parsimonious values are obtained at a cutoff of 77 for subsyndromal depression and 95 for major depression. The choice for using different cutoff scores may depend on the purpose of using the instrument. Overall, the psychometric properties for the PDSS-Spanish Version in Mexican women are similar to the ones obtained in Hispanic women in the United States.