Background/Aims: Vitamin C levels decrease during hemodialysis (HD), which deteriorates antioxidant defense. Vitamin C may also act pro-oxidatively, via reduction in Fe(III). We sought to determine whether intravenous iron (Fe<sub>iv</sub>)-induced oxidative stress differs in HD patients with low and physiological vitamin C levels and whether intravenous vitamin C (C<sub>iv</sub>) administration during HD would change the response to Fe<sub>iv</sub>. Patients and Methods: Twenty patients with vitamin C deficiency (median 15.7 µmol/l, range 8.0–22.7) received Fe<sub>iv</sub> (100 mg iron sucrose between 150 and 180 min of HD). After 4 weeks of oral supplementation, the levels of vitamin C were comparable with those of controls (60.1 µmol/l, range 47.4–70.9). Patients were subsequently treated with (1) Fe<sub>iv</sub>, (2) Fe<sub>iv</sub> and continuous 2 mg/min C<sub>iv</sub> throughout HD, (3) saline (S), and (4) S+C<sub>iv</sub>. Plasma thiobarbituric acid reacting substances (TBARS) and vitamin C were assessed before, during and after FE<sub>iv</sub>(S), and 15, 30 and 60 min after infusion. Results: Fe<sub>iv</sub> induced a comparable rise in TBARS in patients with vitamin C deficiency (before Fe<sub>iv</sub>, 1.9 µmol/l, range 1.4–1.9; after Fe<sub>iv</sub>, 2.6 µmol/l, range 2.3–2.9; p < 0.01) and in those with normal vitamin C (before Fe<sub>iv</sub>, 1.9 µmol/l, range 1.7–2.1; after Fe<sub>iv</sub>, 2.6 µmol/l, range 2.5–2.9; p < 0.01). Fe<sub>iv</sub>+C<sub>iv</sub> resulted in a greater increase in TBARS (after Fe<sub>iv</sub>, 3.1 µmol/l, range 2.8–3.2) compared with Fe<sub>iv</sub> (p < 0.01). Conclusion: Iron sucrose-induced oxidative stress is comparable in HD patients with vitamin C deficiency and in those with normal vitamin C. We documented a pro-oxidative effect of vitamin C during Fe<sub>iv</sub>+C<sub>iv</sub> administration.