Description:Psoriasis is an immune-mediated and chronic inflammatory skin disease Previous research on exploring psoriasis biomarkers using metabolomics lacks a validation step. Moreover, short peptide information in these studies was not investigated. Here, we conducted a comprehensive HILIC-HRMS-based plasma metabolomics study on different population sets, including healthy controls, psoriasis, and urticaria patients. With the aim of identifying potential biomarkers specific to psoriasis, the study design included a discovery step, a validation step, and a further refinement step using urticaria samples. We identified 9 potential biomarkers specific to psoriasis, with 5 being structurally characterized. Two dipeptide biomarkers, γ-GluSer and ThrGly, along with a lysine glycation metabolite, Fruc-Lys, were found to be associated with psoriasis for the first time. Receiver operating characteristic curve analysis revealed all these 9 biomarkers with AUC values above 0.80. A biomarker panel comprising ThrGly and Fruc-Lys demonstrated high diagnostic accuracy (AUC=0.95) in distinguishing psoriasis patients from healthy controls.