Background/aim Acute cerebral infarction (ACI) occurs as a result of instant disruption of vascular flow that causes disbalance between oxidative/antioxidative activity. We examined the relationship of serum neuro-oxidative stress parameters with stroke severity and infarct volume in ACI and emphasized the qualitative importance of high-density lipoprotein (HDL) on its relationship with myeloperoxidase (MPO) and paraoxonase-1 (PON1) in the acute period of stroke. Materials and methods One hundred ACI patients applied within the first 24 h and 50 healthy volunteers were included. The patient group was evaluated with demographic data (including arrival serum biochemical assessment), clinical disability scores, infarct volume, serum oxidative/antioxidative parameters (lipid hydroperoxide (LOOH), MPO, PON1, MPO/PON ratio). The relevant serum parameters were compared with the control group. Dysfunctional HDL measurement was based on detecting dysfunctionality as a result of a high positive correlation between the dysfunctional feature of HDL and the MPO/PON ratio. The correlation of serum parameters, clinical disability score, and infarct volume were evaluated, and independent analyses of variability with comorbidities were performed. Results A negative correlation between PON1 and arrival NIH score/scale (NIHSS), LOOH and discharge modified rankin scale (mRS), triglyceride level, and infarct volume; a positive correlation between MPO\PON ratio and infarct volume was determined. Logistic regression analyses showed that hypertension, diabetes, and high HbA1C may be predictors of stroke severity, and diabetes mellitus, high HbA1C, infarct volume, and high NIHSS score may be predictors of early disability (p < 0.005). The ROC curve analysis revealed that determining the cut-off value for LOOH is of importance in determining early disability scores (7.2 and 6.2, respectively). Conclusion The balance between oxidative and antioxidative stress parameters and their quantitative/qualitative changes is of importance, especially in the acute period of ACI. Dysfunctional HDL’s evolution and its relationship with other oxidants are significant not only in the cardiovascular aspect but also in the clinicoradiological aspect.