Introduction. Prenatal diagnosis of Down syndrome (DS) is based on thecalculated risk of maternal age, biochemical and ultrasonographic markers andrecently by cfDNA. Differences in proteomic profiles may give an opportunity tofind new biomarkers.Objective. Characterize proteome of serum of mothers carrying DS fetus.Material and methods. Blood serum samples of three groups of women wereobtained, a) 10 non-pregnant, b) 10 pregnant with healthy fetus by ultrasoundevaluation, c) 9 pregnant with DS fetus; Sample preparation was as follow:Albumin/IgG depletion, desalting, and trypsin digestion; the process wasperformed in nanoUPLC MS/MS. Data analysis was made with Mass Lynx 4.1and ProteinLynx Global Server 3.0, peptide and protein recognition by MASCOTalgorithm and UNIPROT-Swissprot database.Results. Each group showed different protein profiles. Some proteins were sharedbetween groups. Only sera from pregnant women showed proteins related toimmune and clot pathways. Mothers with DS fetus had 42 specific proteins.Conclusions. We found a different serum protein profile in mothers carrying DSfetuses that do not reflect expression of genes in the extra chromosome. Furtherstudies will be necessary to establish the role of these proteins in aneuploid fetusand analyze their possible use as potential biomarkers