Objective The arterial concentration of carboxyhemoglobin (CO-Hb) in subjects with inflammatory pulmonary disease is higher than that in healthy individuals. We retrospectively analyzed the relationship between the CO-Hb concentration and established markers of disease severity in subjects with interstitial lung disease (ILD). Methods The CO-Hb concentration was measured in subjects with newly diagnosed or untreated ILD and the relationships between the CO-Hb concentration and the serum biomarker levels, lung function, highresolution CT (HRCT) findings, and the uptake in gallium-67 (67Ga) scintigraphy were evaluated. Results Eighty-one non-smoking subjects were studied (mean age, 67 years). Among these subjects, (A) 17 had stable idiopathic pulmonary fibrosis (IPF), (B) 9 had an acute exacerbation of IPF, (C) 44 had stable non-IPF, and (D) 11 had an exacerbation of non-IPF. The CO-Hb concentrations of these subjects were (A) 1.5 +/- 0.5%, (B) 2.1 +/- 0.5%, (C) 1.2 +/- 0.4%, and (D) 1.7 +/- 0.5%. The CO-Hb concentration was positively correlated with the serum levels of surfactant protein (SP)-A (r=0.38), SP-D (r=0.39), and the inflammation index (calculated from HRCT; r=0.57) and was negatively correlated with the partial pressure of oxygen in the arterial blood (r=-0.56) and the predicted diffusion capacity of carbon monoxide (r=-0.61). The CO-Hb concentrations in subjects with a negative heart sign on 67Ga scintigraphy were higher than those in subjects without a negative heart sign (1.4 +/- 0.5% vs. 1.1 +/- 0.3%, p=0.018). Conclusion The CO-Hb levels of subjects with ILD were increased, particularly during an exacerbation, and were correlated with the parameters that reflect pulmonary inflammation.