ABSTRACT: Psoriasis is a common and chronic inflammatory skin disease complicated by genetic-environmental interactions. Although genomic, transcriptomic and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes, such as cell proliferation, apoptosis, immunity, angiogenesis and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-quadrupole tandem mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and detected. Statistical analysis was applied to find different features between the disease and control groups. In addition, ELISA was performed to examine differentially-expressed lipids in psoriatic patient plasma. We finally identified several differential expression lipids including LPAs, LysoPCs, PIs, PCs and PAs, among these metabolites, LPAs, LysoPCs and PAs were significantly increased, while PCs and PIs were down-regulated in psoriasis group. We found that elements of the glycerophospholipid metabolism, such as LPAs, LysoPCs, PAs, PIs, and PCs, were significantly altered in the plasma of psoriatic patients. This investigation characterizes the circulating lipids in psoriatic patients and provides novel insights into the pathogenesis of psoriasis.