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Hidradenitis suppurativa (HS) is an inflammatory skin condition that is often considered a systemic disease due to its association with metabolic comorbidity. In this study, we aimed to identify differences in plasma lipidomic profiles between HS patients and control subjects. HS patients were recruited from a tertiary dermatological centre and demographic and comorbidity matched controls from the general population. A targeted lipidomic approach was performed to characterize over 700 lipid species representing 35 lipid classes/sub-classes. Linear regression models adjusted for confounding factors were used to compare the plasma lipidomic profiles of HS patients to controls. Ordinal regression models were used to study the association of lipids with disease activity and severity scores. 60 HS patients and 73 control subjects were recruited. Differential levels (p < 0.05) of 32 lipid species in HS patients compared to controls were observed, including a decrease in the long chain base d19:1 containing ceramides, and elevation of hydroxyeicosatetraenoic acid (HETE) and dihydroxyeicosatrienoic acid (DHET) oxylipins. These lipids along with several other molecules showed associations with Hurley, HS-PGA and disease activity scores. This study found mild changes in plasma lipidomic profiles, consistent with previous studies showing attenuated metabolomic changes in plasma as opposed to lesional skin. However, a number of lipid species were associated with increasing activity and severity of the disease. Further, the significant lipid species within the same class showed consistent trends of increase or decrease in HS as compared to controls. • HS patients have differences in plasma lipidomic profiles compared to controls. • Phospholipid species containing linoleic acid were increased in HS. • Decreases in d19:1 long chain base ceramides were observed. • Increases in the proinflammatory oxylipins were also seen in HS. [ABSTRACT FROM AUTHOR]