Rationale Vitamin D and vitamin D binding protein (DBP) have been associated with COPD and FEV1. There are limited data regarding emphysema and vitamin D and DBP. Objective This is a pilot study of a portion of the subjects in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study designed to examine the relationship between vitamin D status, DBP, FEV1 and emphysema in COPD patients. Methods We measured serum 25(OH)D and DBP in 498 ECLIPSE subjects. Subjects were distributed amongst smoker controls, non-smoker controls, and GOLD stages 2, 3 and 4. Within each GOLD stage, the subjects were equally divided amongst high and low emphysema burden. The associations between 25(OH)D, DBP, and free vitamin D with FEV1, CT-defined emphysema, biomarkers and clinical data including CT-measured bone attenuation were assessed. Measurements 25(OH)D and DBP were measured using tandem mass spectroscopy and competitive enzyme-linked immunosorbent assay, respectively, Main result 25(OH)D was correlated with FEV1 (p = 0.01) and with severity of emphysema (p < 0.01). 25(OH)D was also associated with six-minute walk (p = 0.02), bronchodilator response (p = 0.04), and Clara cell secretory protein (CC-16) (p = 0.01). 25(OH)D levels were not associated with CT-measured bone attenuation, however DBP was associated with bone attenuation in subjects with emphysema. DBP was not associated with FEV1 or emphysema. 25(OH)D and DBP were inversely associated (p = 0.01). Conclusion This is the first study to demonstrate a relationship between emphysema and vitamin D. We also provide further evidence for a relationship between vitamin D and FEV1.