Current needs in veterinary medicine and animal husbandry include the identification of tools that allow the early warning of diseases, especially during the incubation periods and before the onset of clinical signs. Therefore, the objective of this study was to identify by SELDI-TOF MS a proteomic profile able to differentiate PPRSV-positive from -negative weaning piglets raised in commercial farms and without clinical symptoms of the disease. We optimized the experimental conditions previously described [20] and validated 47 statistically significant discriminatory biomarkers. Among these, a combination of 14 biomarkers identified in F1 on CM10 at low focus mass permitted to correctly assign the piglets to the PPRSV-positive or PRRSV-negative groups with sensitivity and specificity of 77% and 73%, respectively.