Background This study aimed to investigate whether serum indicators related to iron stores in the body are associated with clinical and endoscopic disease severity. Methods Eighty-four patients with Crohn’s disease (CD) and twenty-four healthy volunteers were included in this retrospective study. Clinical and endoscopic severity of disease was recorded by Crohn’s disease activity index (CDAI) scores and the simple endoscopic score of Crohn’s disease (SES-CD), respectively. The indicators related to iron stores included serum iron (SI), total iron binding capacity (TIBC), ferritin, transferrin (Tf), and transferrin saturation (TSAT%). They were detected within one week after endoscopic and CT enterography examinations. Results Patients were divided into three groups according to the CDAI scores. Serum iron levels were decreased in all patient groups (p p p p p > 0.05). Underweight, decreased serum iron and TIBC were independent risk factors for moderate clinical disease. Combined detection of decreased serum iron and TIBC was helpful in differentiating severe patients. The sensitivity and specificity were 32.7% and 100%, respectively (AUC = 0.812, p