Psoriasis is a prevalent inflammatory dermatosis with possible systemic involvement. Metabolomics defines as an extensive study of all low molecular weight metabolites in human body which has recently led to better understanding of the pathogenesis of different disease. To evaluate the targeted lipidomics in sera of patients versus healthy controls. The study included 64 patients with psoriasis and 64 age- and sex-matched healthy controls. All the participants underwent a targeted lipidomics on their sera using Gas Chromatography with flame-ionization detection (GC-FID). The clinical importance of serum level of lipids was also dealt with. Serum level of all tested fatty acids (except for METHYL VACCENATE) in patients was higher than healthy controls, though this difference was significant only for METHYL PALMITATE, METHYL OLEATE and METHYL LINOLEATE (P values: 0.002, 0.001 and 0.001 respectively). Based on our results, the serum levels of METHYL OLEATE, METHYL LINOLEATE, METHYL PALMITATE and METHYL STEARATE could significantly be used for predicting the disease severity (P values: 0.009, <
0.005, 0.02 and 0.001, respectively). METHYL MYRISTOLEATE, METHYL 11-14-17-EICOSATRIENOATE and METHYL LINOLEATE were the fatty acids which their serum levels were significantly predictive of duration of disease (P values: 0.018, <
0.005 and 0.009, respectively). Our findings suggest that circulating specific lipids have different serum levels in psoriasis patients in comparison with healthy controls. We suggest the serum METHYL LINOLEATE as a potential biomarker to evaluate psoriasis severity and prognosis. However, comprehensive, long-term studies are essential for validating its prognostic value.