Sjögren's Syndrome (SjS) is a complex autoimmune disease characterized by the affection of the exocrine glands and the involvement of multiple organs. Although a greater number of biomarker studies have been carried out in recent years, the origin and pathogenesis are not yet well known and therefore there is a need to continue studying this pathology. This work aims to find metabolic changes in biological samples (plasma and urine), which could help identify the metabolic pathways affected by the SjS pathogenesis. The samples collected from SjS patients and healthy volunteers were analyzed by a fingerprinting metabolomic approach based on HPLC-ESI-QTOF-MS methodology. After feature pre-selection by univariate statistical tests, an integrated PLS-DA model using data from urine and plasma was constructed obtaining a good classification between cases and controls (AUROC = 0.839 ± 0.021). 31 and 38 metabolites in plasma and urine, respectively, showed significant differences between healthy volunteers and SjS patients and were proposed for their identification. From them, 12 plasma and 24 urinary metabolites could be annotated. In general, the main metabolic pathways altered in SjS patients were related to the metabolism of phospholipids, fatty acids, and amino acids, specially tryptophan, proline and phenylalanine.