The aim was to use metabolomics to compare metabolic reactions to acute stress between clinical burnout patients and healthy individuals. Fifteen burnout patients (6 women) and 15 controls (8 women) performed the Trier Social Stress Test (TSST). Plasma samples taken before and directly after the TSST were analyzed for metabolite content using gas chromatography time of flight mass spectrometry (GC-TOF-MS). Metabolomics data were analyzed using orthogonal partial least squares-effect projections (OPLS-EP).