BACKGROUND: The impact of iron deficiency on COPD morbidity independent of anemia status is unknown. Understanding the association between iron deficiency, anemia status, and risk of hospitalization in COPD may inform an approach to these comorbidities. STUDY DESIGN AND METHODS: Adults ≥40 years from the Johns Hopkins COPD Precision Medicine Center of Excellence data repository with an outpatient iron profile and 1 year of subsequent follow-up time were included in the study. Baseline characteristics were compared across iron status, defined by transferrin saturation (TSAT), using RESULTS: There were 6532 individuals included with an average age of 65±12 years, 59% were female, and 56% White. Fifty-two percent of the cohort were iron deficient (TSAT≤20%), among whom 27% were non-anemic. Iron-deficient individuals had lower lung function and a higher prevalence of heart failure and diabetes. Iron deficiency was more prevalent among females (57%) compared to males (44%). In adjusted models, a decrease in TSAT by 10% was associated with 14.3% higher odds of all-cause hospitalization for females (95%CI:1.0-1.3), but not among males (OR:1.08, 95%CI:0.9-1.3). There was effect modification by anemia such that the association between TSAT and all-cause hospitalization was greater in non-anemic women ( INTERPRETATION: Iron deficiency may be associated with adverse outcomes in the absence of anemia, with non-anemic women being a COPD sub-population particularly sensitive to iron deficiency.