INTRODUCTION: It has been observed that intravenous iron administration may suppress endogenous production of erythropoietin (EPO). We postulate that this effect may be mediated by increased FGF-23 secretion. AIM OF THE STUDY: To evaluate the short-term effect of intravenous iron sucrose administration on endogenous EPO secretion in patients with chronic kidney disease (CKD). MATERIALS AND METHODS: The cohort comprised 35 nondialysis patients with CKD stages 3-5. All received 100 mg of intravenous iron (III)-hydroxide sucrose complex daily for five consecutive days. Plasma EPO, iFGF-23, cFGF-23, PTH, bone alkaline phosphatase (BAP), phosphorus (PO4), calcium (Ca), and high-sensitive C-reactive protein (CRP) were measured before, and two hours after, the first and third iron infusions, and after completing iron therapy. RESULTS: EPO concentration at the end of iron treatment was significantly lower than two hours after the first iron infusion ( = 0.0003) and before the third dose ( = 0.0006) (12.6 [10.2, 41.4] mIU/mL. vs. 30.9 [15.9, 54.2] mIU/mL and 33.4 [15.4, 56.7] mIU/mL, respectively). Conversely, plasma iFGF-23 was significantly higher before the third dose (61.1 [18.6, 420.1 4] pg/mL;  = 0.025) and after the course of treatment (92.1 [28.4, 878.1] pg/mL;  = 0.004) compared to pretreatment value (48.4 [16.2, 420] pg/mL). cFGF-23 concentration was significantly lower than baseline after the first iron dose (491.8 [257.7, 1086.3] vs. 339.2 [75.4, 951.2] RU/mL;  = 0.005) and after treatment (398.7 [90.4, 1022.3] RU/mL;  = 0.025). No significant linear correlation was found between changes in plasma EPO and FGF-23. CONCLUSIONS: Although intravenous iron therapy causes parallel increase of FGF-23 and supression of endogenous EPO, these two effects seem to be independent.