Abstract Background It is well established that inflammation can mimic some aspects of iron deficiency (ID) by impairing the utilisation of existing iron stores for red cell production and inducing an iron-sequestration syndrome and hypoferraemia. Diagnosis of ID is therefore complex and there is currently no standard clinical test capable of clearly distinguishing ID when inflammation is present. Often, a combination of parameters is necessary. The aim of this study was to investigate which sole parameter or combination of parameters can best predict ID in patients with IBD. Methods A cross-sectional study was conducted using routine blood samples from patients with IBD. Blood samples were analysed for standard blood count, iron status (serum ferritin; SF, transferrin saturation; TSAT), inflammation parameters (high sensitivity C-reactive protein; hsCRP) and soluble transferrin receptor (sTfR) using standard methodology. A multiparameter index test (MCV, TSAT, SF) was performed to define patients with iron restricted erythropoiesis (IRE) (IRE group) when at least 2 of the 3 parameters indicated IRE. Cut-off values for TSAT (<20%) and SF (<30/μL) were defined according to ECCO guidelines and for MCV (80 fL) according to the literature. Criteria taken to indicate absolute ID (AID) were hsCRP <5 mg/L, SF 30 μg/L and TSAT < 20%, while functional ID (FID) was denoted by hsCRP ≥ 5 mg/L, SF < 100 μg/L and TSAT < 20%. Results 168 IBD patients (88f; 85CD/83UC;43.4±14.9y) were enrolled. Of these, 107/168 had inflammation. 100/168 patients had IRE, of whom 70/100 had FID and 30/100 had AID. ROC analysis was performed to compare different parameters as detectors of IRE and to summarise the performance of each respective parameter (Table 1). When inflammation was absent, the best combination was SF and TSAT, whereas in the presence of inflammation, the best combination was found to be TSAT and sTfR. The addition of MCV, which showed high specificity regardless of inflammation, was found to add additional value to the diagnosis in the context of inflammation (p <0.001). Conclusion Of those parameters studied, none was suitable to diagnose IRE when taken alone. In the absence of inflammation, ID in IBD can be adequately determined by combining SF and TSAT. When inflammation is present, however, the combination of TSAT with sTfR measurement was found to be more accurate, while the additional inclusion of MCV added additional value to the diagnosis.