BackgroundAnemia is associated with impaired physical performance and adverse perioperative outcomes. Iron-deficiency anemia is increasingly treated with intravenous iron before elective surgery. We explored the relationship between exercise capacity, anemia, and total hemoglobin mass (tHb-mass) and the response to intravenous iron in anemic patients prior to surgery.MethodsA prospective clinical study was undertaken in patients having routine cardiopulmonary exercise testing (CPET) with a hemoglobin concentration ([Hb]) < 130 g.l−1and iron deficiency/depletion. Patients underwent CPET and tHb-mass measurements before and a minimum of 14 days after receiving intravenous (i.v.) Ferric derisomaltose (Monofer®) at the baseline visit. Comparative analysis of hematological and CPET variables was performed pre and post-iron treatment.ResultsTwenty-six subjects were recruited, of whom 6 withdrew prior to study completion. The remaining 20 (9 [45%] male; mean ± SD age 68 ± 10 years) were assessed 25 ± 7 days between baseline and the final visit. Following i.v. iron, increases were seen in [Hb] (mean ± SD) from 109 ± 14 to 116 ± 12 g l−1(mean rise 6.4% or 7.3 g l−1,p=  < 0.0001, 95% CI 4.5–10.1); tHb-mass from 497 ± 134 to 546 ± 139 g (mean rise 9.3% or 49 g,p=  < 0.0001, 95% CI 29.4–69.2). Oxygen consumption at anerobic threshold (\documentclass[12pt]{minimal}
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				\begin{document}$$\dot{\text{V}}$$\end{document}V˙O2 AT) did not change (9.1 ± 1.7 to 9.8 ± 2.5 ml kg−1min−1,p= 0.09, 95% CI − 0.13 − 1.3). Peak oxygen consumption (\documentclass[12pt]{minimal}
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				\begin{document}$$\dot{\text{V}}$$\end{document}V˙O2 peak) increased from 15.2 ± 4.1 to 16 ± 4.4 ml.kg.−1min−1,p= 0.02, 95% CI 0.2–1.8) and peak work rate increased from 93 [67–112] watts to 96 [68–122] watts (p= 0.02, 95% CI 1.3–10.8).ConclusionPreoperative administration of intravenous iron to iron-deficient/deplete anemic patients is associated with increases in [Hb], tHb-mass, peak oxygen consumption, and peak work rate. Further appropriately powered prospective studies are required to ascertain whether improvements in tHb-mass and performance in turn lead to reductions in perioperative morbidity.Trial registrationClinicalTrials.gov identifier: NCT 033 46213.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13741-023-00319-x.