Chronic Obstructive Pulmonary Disease (COPD), a lung disease related to smoking, is one of the leading causes of chronic morbidity and mortality around the world. One goal in COPD research is the identification of biomarkers for early diagnosis of the disease. Here, we sought COPD-specific changes in the proteome from human lung tissue. This revealed increased levels of surfactant protein A (SP-A) in COPD but not in the normal or fibrotic lung. The results were confirmed by immunohistochemistry, morphometry and Western blotting. Furthermore, elevated SP-A protein levels were detected from the induced sputum supernatants of COPD patients. The levels of other surfactant proteins (SP-B, SP-C, SP-D) were not altered. Our results suggest that SP-A is linked to the pathogenesis of COPD and could be considered as a potential COPD biomarker.