Hidradenitis suppurativa (HS) is a chronic, inflammatory, immune-mediated skin disease associated with several comorbidities and vascular risk factors. Oxidative stress, inflammation, and altered high-density lipoprotein (HDL) functions play key roles in inflammatory skin diseases. However, the relationship between these factors and HS is not fully understood. The aim of this study was to investigate the relationship between HS and oxidative stress, inflammation, and HDL functions, focusing on inflammatory markers and HDL-related antioxidant properties. We evaluated the serum levels of inflammation markers serum amyloid A (SAA) and monocyte chemoattractant protein-1 (MCP-1) in 44 HS patients and 16 healthy controls. Additionally, we assessed the activity of the antioxidant enzyme paraoxonase-1 (PON1) associated with HDL, as well as the HDL redox properties using a cell-free method. HS patients showed significantly higher serum levels of MCP-1 and SAA compared to controls. PON1 activity was considerably lower in HS patients, suggesting impaired antioxidant functions of HDL. These changes in HDL correlated with the severity of HS but occurred without significant alterations in plasma HDL levels. Our findings indicate that inflammation and oxidative stress could contribute to the dysfunction of HDL in HS patients. Identifying dysfunctional HDL could provide valuable insights into the pathogenesis of HS and its associated complications, offering potential targets for new therapeutic strategies.