We found that (a) AIS is characterized by lower chloromethyl acetate CMPAase PON1 activity, HDL and -SH groups and increased LOOH and neurotoxicity (a composite of LOOH, inflammatory markers and glycated hemoglobin); (b) oxidative and antioxidant biomarkers strongly and independently predict mRS scores 3 and 6 months later, DWI stroke volume and FLAIR signal intensity; and (c) the PON1 Q192R variant has multiple effects on stroke outcomes that are mediated by its effects on antioxidant defenses and lipid peroxidation. Here, PON1 is linked to Stroke.