Objective: Preeclampsia (PE) is a leading cause of pregnancy-associated maternal and neonatal morbidity and mortality. Detection of patients at risk before the clinical onset of PE is a priority. Proteomics have become a valuable tool for the discovery of new biomarkers; however, the understanding of the underlying mechanism is necessary. The aim of the study was to deter mine differences between proteomic serum profiles of PE and normotensive pregnancies using quantitative and qualitative approaches. Study design: Serum samples from pregnant women were taken at 10–12 weeks of gestation with follow-up to determine PE development. Samples were analyzed using nano 2-D liquid chromatography UPLC and qTOF-MS/MS. Results: A total of 136 women were recruited, of which eight (5.9%) developed PE, and eight normotensive were randomly selected as a control group for comparison. A different profile was obtained between groups. Nine proteins showed quantitative differences with fold-change over 1.5: PRRC2C (217.02), HEATR5A (179.46), ATP6 (162.38), PRRC2B (83.09), RBM25 (5.36), NUP205 (3.38), HLA-I (2.27), ZC3H13 (2.15), and SREK1 (1.66); and two under 0.66: Importin-4 (0.55) and Cytochrome b (0.26). Using bilateral Fisher’s exact test for the qualitative approach, LRRK1 had statistical significance (p ¼ .044), while PRRC2B (p ¼ .121), PRRC2C (p ¼ .134), and NUP205 (p ¼ .134) showed a tendency to be present in PE. Conclusion: The found proteins have plausibility with the early pathophysiological events that have been associated with this pathology. Further studies should be performed to confirm these findings and elucidate their specific roles