Schizophrenia is one of the most severe psychiatric disorders affecting 1% of the world population. There is yet no empirical method to validate the diagnosis of the disease. The identification of an underlying molecular alteration could lead to an improved disease understanding and may yield an objective panel of biomarkers to aid in the diagnosis of this devastating disease. Presented is the largest reported liquid chromatography-mass spectrometry-based proteomic profiling study investigating serum samples taken from first-onset drug-naive patients compared with samples collected from healthy volunteers. The results of this large-scale study are presented along with enzyme-linked immunosorbent assay-based validation data.