Hepatitis C virus (HCV) is a public health problem in Egypt where about 20% of the population suffer from HCV infection, which represents the highest prevalence in the world. Moreover, up to 50% of hemodialysis (HD) patients in Egypt are HCV seropositive. Increased levels of oxidants and lower levels of antioxidants in ESRD patients play an important role in the development of endothelial dysfunction, atherogenesis and CVD. Over the past few years, the measurement of F2-isoprostanes (IsoPs) have emerged as one of the most sensitive and reliable biomarkers of lipid peroxidation in vivo and in vitro. Oxidative stress (OS) markers among HD patients with HCV infection was widely studied with controversial results. Our aim was to study in depth the relationship between plasma 8-ISO-prostaglandin F2 alpha (8-iso-PGF2α) as an oxidative stress marker and HCV infection in HD patients. 88 ESRD patients on maintenance HD. Participants were recruited from three HD centers (Alexandria Main University hospital, Al Mowasat University Hospital and Smoha University Hospital). Patients were divided into two groups according to the presence (HCV+) or absence (HCV−) of serum antibodies against HCV. No patients with hepatitis C were undergoing antiviral treatment at enrollment. Treatment with anti-oxidant, Smoking, Active inflammatory or infectious diseases, Diabetes Mellitus and active liver disease were excluded from the study. Midweek predialysis session blood samples were drawn for measurement of high sensitivity CRP (HsCRP), intact parathyroid hormone (PTH) and 25(OH) vitamin D. Plasma 8-iso-PGF2α was measured by sandwich enzyme linked immunosorbent assay (ELISA) technique. On the same day common carotid intima media thickness (CIMT) was measured using B-mode ultrasound. Of the 88 patients enrolled 35 patients (39.8%) were HCV positive. No significant difference regarding age, sex, calcium and phosphorus was observed between the 2 groups. 8-iso-PGF2α was significantly lower in the HCV+ve group compared to the other group (405.6 ± 455.9 pg/mL vs. 759.0 ± 552.4 pg/mL, p<0.002), 8-iso-PGF2 was also significantly correlated with the duration of HD (r:-0.229, p<0.032). HsCRP and CIMT were elevated in both patients but were not significantly different between both groups (7.50 ± 7.70 mg/l vs 6.95 ± 6.97 mg/l, p =1.000; 0.83 ± 0.21 cm vs 0.82 ± 0.26 cm, p =0.813, respectively). CIMT was not significantly correlated with 8-iso-PGF2 and the other studied variables but was only significantly correlated with age (r: 0.489, P<0.001) in the overall sample. The significant lower levels of 8-iso-PGF2α observed among HCV+ patients on hemodialysis compared to seronegative patients irrespective of PTH and Vit.D levels suggests that HCV infection has a protective role against oxidative stress among these populations.