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Objective: The connection of oxidative stress with dyslipidemia creates a newly-emerging atherosclerosis risk factor involved in acute ischemic stroke development. This study analyzed the influence of oxidative stress on structural changes of high-density lipoprotein (HDL) particles connected with modification in protective paraoxonase 1 (PON1) activity., Methods: This study used 185 patients with acute ischemic stroke and 185 apparently healthy controls. Oxidative stress status, PON1 status, lipids and high-sensitivity C-reactive protein (hsCRP) were determined. In isolated HDL lipoprotein fraction we determined selected markers of oxidative stress (malondialdehyde, MDA) and the content of total sulfhydryl (SH) groups. The capability of oxidative and PON1 status parameters to discriminate patients according to survival status was evaluated., Results: Stroke patients had lower HDL-cholesterol than controls and a remarkable fall in PON1 activity (control group-227U/L, survivors-42U/L, lethal outcome group-61U/L, p < 0.001), along with more prominent inflammation. Pronounced oxidative stress and impaired antioxidative protection was present among patients. HDL fraction analysis revealed a significant decrease of SH groups content (control group vs. patients, p < 0.05) and increased in MDA content in patients (lethal outcome vs. control group, p < 0.05). According to logistic regression analysis, the best predictor of disease outcome was oxidative stress marker - prooxidative-antioxidative balance (PAB)., Conclusions: Pronounced oxidative stress in this group of acute ischemic stroke patients probably led to HDL structural changes, which could further cause an alteration or decrease of PON1 activity. Evidence of increased prooxidant level associated with decreased protective, antioxidative factors suggests their mutual involvement in this complex pathology., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)