|Chronic obstructive pulmonary disease (COPD) is an inflammatory disease characterised by emphysema and chronic bronchitis. Cigarette smoke (CS) inhalation constitutes the primary risk factor for COPD progression and dysregulates numerous pathways essential to lung-resident alveolar macrophage (AM) and circulating bone marrow-derived macrophage (BMDM) function. Aberrant iron metabolism is one such hallmark: AMs are the primary lung resident iron-positive cells, with numerous iron-related proteins elevated in patient bronchoalveolar lavage fluid (BALF). Interestingly, CS also causes mitochondrial dysfunction in macrophages, which are the primary iron storage sites in the cell. While CS is known to associate with mitochondrial dysfunction in COPD, its effect on mitochondrial iron in COPD macrophages is unknown. Using an in vitro model of smoke exposure, we show that CS alters expression of the mitochondrial iron transporters mitoferrin 1 and 2 and mitochondrial iron content in BMDMs, with further dysregulation upon lipopolysaccharide treatment. RNAseq of AMs isolated from patient BALF revealed altered expression patterns in vivo, with mitoferrin 1 and 2 expression further studied in AMs isolated from CS-exposed mice. These findings illustrate the role of macrophage mitochondrial iron dysregulation in COPD pathogenesis and present the manipulation of mitochondrial iron in the lung as an intriguing therapeutic target.