Chronic obstructive pulmonary disease (COPD) is caused by chronic inflammation. Many inflammatory mediators induce the low grade systemic inflammation of COPD. Haptoglobin (Hp) is synthesized in the liver and by lung epithelial and alveolar macrophage cells. However, associations of the serum concentration and phenotype of Hp with COPD are unclear. Therefore, we explored the association of the Hp concentration and Hp phenotype with the inflammatory response and COPD disease severity. We included healthy subjects and COPD patients. The Hp phenotype was categorized by SDS native-PAGE, and concentrations were determined by ELISA. In this trial Hp concentrations in COPD groups were significantly higher than those in healthy controls. There was a significant negative correlation between the Hp concentration and FEV1(%) (p < 0.001), while IL-6 and 8-isoprostane were positively correlated with the Hp concentration. As to the Hp phenotype, there were significant negative correlations between the FEV1 and both Hp2-1 and Hp2-2; IL-6 and 8-isoprostane were significantly positively correlated with Hp2-1 and Hp2-2. The ROC curve analysis of the Hp concentration was significantly higher than CRP. Hp concentrations and phenotype were positively correlated with the severity of COPD, especially Hp2-2. In the future, Hp can be considered a novel biomarker for identifying COPD.