Surfactant Protein D (SP-D), a glycoprotein released by type II pneumocytes, reportedly predicts pulmonary functional integrity and disease progression. The aim of this study was to define the relationship between SP-D level and COPD severity. Sixty-three patients with stable COPD and 25 healthy control subjects were enrolled. Demographics and COPD severity according to GOLD 2013 staging criteria were evaluated. Arterial blood gases, pulmonary function tests, and exercise test were performed. CAT score, Charlson Comorbidity Index, St. George’s Questionnaire scores, and BODE index were calculated. The relationship between SP-D level and COPD severity, dyspnea level, and quality of life was investigated. According to GOLD 2013, 30 subjects were in group A, 12 in group B, 12 in group C, and 9 in group D. The serum SP-D level was significantly higher in the COPD group (171.9 ± 113.0 ng/mL) than in the control group (106.8 ± 46.7 ng/mL) (p<0.01). SP-D was significantly correlated to FEV1 (p=0.01) and FEV1/FVC (p<0.01). Furthermore, there was a significant negative correlation between SP-D and carbon monoxide diffusion capacity (p=0.03). There was a statistically significant correlation between SP-D and PaCO2 (p=0.02). High-risk GOLD groups (C and D) had a significantly higher SP-D level than the low-risk groups (A and B) (p=0.01). Serum SP-D level significantly correlated with the BODE index (p<0.01). Serum SP-D was elevated in patients with COPD and associated with impaired lung function, high PaCO2 level and decreased diffusion capacity for carbon monoxide. In addition, the correlation found between serum SP-D levels and the BODE index could reflect the overall severity of COPD.