Background: The aim of the study was to determine the utility of plasma NfH in correlation with serum hsCRP for severity and short-term functional outcome prediction after ischemic stroke. Methods: 124 patients and 40 healthy controls were enrolled, serial plasma neurofilament heavy chains and hsCRP concentrations were measured and evaluated for TOAST subtype, stroke severity and functional outcome at discharge. Results: Serum level of hsCRP was significantly higher in patients versus controls (p<0.05) with no difference between TOAST subtypes. Plasma NfH concentration on day 5 was higher in CE stroke compared to LAA group and SVO group. A positive correlation between NfH levels on day 5 and mRS at discharge (r=0.304, p=0.001) and a gender stratification of hsCRP and mRS at discharge was found. Values of 6.04 mg/l for hsCRP and 46.4 ng/ml for NfH were found predictive for unfavorable short-term outcome, but after adjusting for age, sex and stroke severity, the prediction power was lost. Conclusions: Plasma concentration of NfH shows a significant increase over the first five days after ischemic stroke, in correlation with inflammatory status and short-term evolution.