Background: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder. Relapsing-remitting MS (RRMS) is the most common MS pattern characterized by relapses or exacerbations. This study aimed to investigate the status of serum endothelial NOXs (NOX5 and NOX4) and iron metabolism biomarkers in RRMS patients. Methods: The study was carried out on 40 RRMS patients and 40 control subjects. All the participants were subjected to complete history taking, general and full neurological examination, Serum NOX4,5, ferritin, iron, iron binding capacity, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels were measured in all the study subjects. Results: MS cases showed significantly lower Nox4, significantly higher Nox5 when compared to control group (median =0.081 versus 0.395, p < 0.001; median=3.5 versus 0.225, p < 0.001 respectively). High accuracy AUC was found regarding Nox 4 and Nox 5 (AUC=0.928, 0.988 respectively). At best cut off value of Nox-4 (=0.24 Mmol/L), sensitivity was 90%, specificity was 95%, PPV was 95%, NPV was 90% and accuracy was 92.4%. At best cut off value of Nox-5 (=1.67 Mmol/L), sensitivity was 100%, specificity was 97.5%, PPV was 97.6%, NPV was 100% and accuracy was 98.8%. Conclusion; Our data suggest that increased NOX5 expression and decreased levels of NOX4 might be related with oxidative stress related vascular changes and BBB disruption in MS patients.