BACKGROUND With the recent implementation of bundling reimbursement policy, the use of intravenous (IV) iron preparations for the management of anemia in the end-stage renal disease (ESRD) population has dramatically increased. Iron overload increases the risk of infections in individuals with or without kidney disease. IV iron administration in ESRD patients impairs bacteriocidal capacity of polymorphonuclear leukocytes (PMNs) against Escherichia coli. These preparations consist of an elemental iron core and a carbohydrate shell. In addition to the iron core, the carbohydrate shell may affect PMNs. We therefore examined the effect of iron sucrose, a commonly used preparation, on phagocytic capacity of PMNs from a group of normal individuals against Gram-positive (Staphylococcus aureus) and Gram-negative (E. coli) bacteria. METHODS Iron sucrose was added to heparinized blood samples at pharmacologically-relevant concentrations and incubated for 4 and 24 h at 37°C to simulate in vivo condition. Blood samples mixed with equal volume of saline solution served as controls. To isolate the effects of the carbohydrate shell, blood samples were co-treated with the iron chelator, desferrioxamine. RESULTS Iron sucrose caused significant PMN apoptosis and dose-dependent suppression of phagocytic function against both Gram-positive and Gram-negative bacteria. These abnormalities were prevented by desferrioxamine which precluded contribution of the carbohydrate shell to the PMN dysfunction. CONCLUSIONS At pharmacologically-relevant concentrations, iron sucrose promotes apoptosis and inhibits phagocytic activities of PMNs. The deleterious effect of iron sucrose is mediated by its elemental iron core, not its carbohydrate shell, and as such may be shared by other IV iron preparations.