Although a combination of peaks identified with different experimental conditions (e.g. using different fractions and different surfaces) might have provided higher discriminatory power, here we developed a PRRSV diagnostic test based on peaks identified with the same experimental conditions (e.g. fraction, surface, and focus mass), which can be reproduced at high-throughput at reasonable costs. These results provide a set of proteomic biomarkers and related, optimized experimental conditions for high-throughput profiling of pig populations by SELDI-TOF MS for whole genome association studies, where identification of proteins underlying the phenotype can be made a posteriori. SELDI-TOF MS might therefore represent a complementary test or a possible alternative to classical (PCR) and more recent diagnostic methods (e.g. antibody detection in saliva) for profiling large flocks of pigs at reasonable costs, using blood samples that are routinely collected for general veterinary inspections. As well, these SELDI-TOF MS based tests could complement and provide a broader reference for emerging diagnostic methods and have potential applications for the detection of relevant proteins having highly heritable traits (e.g. acute phase proteins).