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Purpose: Assess whether iron deficiency prevalence in heavy smokers is higher in presence of COPD and/or emphysema, how the prevalence of iron deficiency is impacted by the biomarker used to define it, and examine the prevalence of anemia and polycythemia in heavy smokers with or without COPD. Patients and Methods: A cross-sectional analysis was conducted on 1002 participants from the Norwegian Early Lung Cancer Screening study. All participants underwent chest CT scans, spirometry, and venous blood sampling to analyze iron-related parameters, C-reactive protein (CRP), and hemoglobin. Iron deficiency was defined using transferrin saturation (TSat) < 20%, ferritin < cutoff (CRP-dependent), or a combination of both. Results: The prevalence of iron deficiency varied from 3% to 30%, being highest when defined by TSat < 20%, and was more prevalent in participants with COPD. Emphysema was not associated with iron deficiency. Decreasing hemoglobin, increasing soluble transferrin receptor (sTfR) and CRP were associated with TSat < 20%. COPD was not independently associated with iron deficiency. Increasing age and sTfR, along with female sex, were associated with ferritin < cutoff. Anemia was more common than polycythemia, with approximately one-third of anemia cases attributable to iron deficiency. Conclusion: Iron deficiency was more prevalent in heavy smokers with COPD than in those without, but not in individuals with emphysema. TSat < 20% identified significantly more cases of iron deficiency than ferritin < cutoff. Eight percent of participants had anemia, while four percent had polycythemia, with neither condition related to COPD or emphysema. Keywords: comorbidity, COPD, iron deficiency, smoking