<p>Psoriasis (PS) is a chronic inflammatory skin disease associated with cardiometabolic comorbidity. While systemic inflammation is recognized as a major driver of this risk, metabolomic signatures linking PS to cardiometabolic dysfunction remain incompletely defined. The aim of this study was to characterize the serum metabolomic profile of PS and identify metabolic alterations that may contribute to cardiometabolic risk. Fasting serum samples from 455 individuals with PS and 591 matched controls were measured using proton NMR spectroscopy. A total of 325 biomarkers including lipoproteins, fatty acids, amino acids, apolipoproteins, inflammation-related metabolites and their ratios were quantified. PS demonstrated an atherogenic metabolic signature characterized by increased LDL, ApoB, triglyceride-rich VLDL, and small HDL/LDL subclasses. Elevations in saturated, monounsaturated, and omega-6 fatty acids–including linoleic acid were observed, alongside increases in histidine and valine and decreases in glycine and phenylalanine. Differential correlation and interaction analyzes revealed extensive remodeling of the metabolic network architecture in psoriasis. It can be concluded that PS is associated with coordinated disturbances across lipid, fatty-acid, and amino-acid pathways, reflecting a systemic pro-atherogenic and pro-inflammatory environment. These metabolomic alterations provide mechanistic insight into heightened cardiometabolic risk and highlight potential biomarkers for disease stratification and future interventional studies.</p>