Objectives: The research objective was to determine the prevalence of iron deficiency as a possible cause of suboptimal response to cardiac resynchronization therapy (CRT) and to establish the association of sideropenia with the clinical presentation. Materials and methods: A cross-sectional clinical study included 121 patients with heart failure undergoing CRT who provided informed consent to participate. The patients underwent a clinical examination, blood samples were taken and comprehensive demographic and medical history data were obtained. Results: The prevalence of sideropenia is 55%, and the prevalence of anemia of any cause is 20.4%. The most common iron-related disorder is prelatent sideropenia (27%), and the prevalence of sideropenic anemia is 4.5%. Patients with sideropenia do not differ from patients without sideropenia in general demographic (age, gender, BMI) or basic clinical (duration of treatment, device type, baseline rhythm, frequency of previous hospitalizations, blood pressure) indicators, but they have a higher prevalence of arterial hypertension (P=0.001) and type II diabetes (P=0.011), and they use statin therapy more frequently (P=0.030). OMT was achieved in 69.4% of patients. Patients with sideropenia more frequently belong to higher NYHA functional classes (P=0.024) and have significantly higher levels of NT-proBNP (P=0.034). Poorer clinical presentation is also associated with lower levels of hemoglobin, hematocrit, and serum iron, as well as higher levels of RDW and hypochromic red blood cell proportion. Lower transferrin saturation levels in higher NYHA functional classes are marginally significant. Additionally, patients in higher NYHA classes have a significantly higher prevalence of concurrent anemia and sideropenia, while in lower NYHA classes, most patients have neither anemia nor sideropenia (P=0.011). Conclusion: A high prevalence of sideropenia as a common reversible cause of suboptimal response to CRT and its significant association with the poor cardiopulmonal status of these patients have been confirmed. Timely diagnosis and treatment of sideropenia are of utmost importance to limit the negative effects that sideropenia has on the effectiveness of cardiac resynchronization therapy in patients with heart failure.