The aim of this study was to characterize the salivary metabolomic profile in adolescents with juvenile systemic lupus erythematosus (jSLE). A total of 24 adolescents with jSLE (15.92 ± 2.06 years) and 12 systemically healthy controls (15.25 ± 2.7 years) were included in the study. Participants underwent rheumatologic testing and periodontal examination, with the recording of plaque index (PI), probing depth (PD), clinical attachment level (CAL), and bleeding on probing index (BPI). Unstimulated whole saliva was collected from both groups and stored at -80 ºC. The salivary proton nuclear magnetic resonance ( 1 H-NMR) spectra were acquired in a spectrometer operating at 500 MHz. Partial least squared discriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) were used for statistical analysis. Mean CAL and PI were significantly increased in the group with jSLE (p < 0.01). Patients with jSLE presented a significantly different salivary metabolic profile (accuracy = 0.54; R² = 0.86; Q² = -0.293), significantly higher salivary levels of N-acetyl sugars, and significantly reduced levels of phenylalanine, glycine, taurine, hydroxybutyrate, and valerate compared with healthy controls (p < 0.05). It is suggested that the salivary metabolomic profile analyzed by ¹H NMR in patients with jSLE presents a different fingerprint that the systemically healthy subjects. Integrating the variation of metabolites with the identification of the metabolic pathways involved seems to provide a better understanding of the influence of systemic disease on salivary metabolites.