Background: The most important pathogenic mechanisms involved in the development of chronic obstructive pulmonary disease (COPD) are protease-antiprotease imbalance, inflammation, lung remodeling and oxidative stress. Interestingly, lower vitamin D levels have been related to regulation of each of these processes, that is, higher expression of proteases, modulation of inflammation, modulation of extracellular matrix turnover, and increased oxidative stress. Thus, one can speculate that lower vitamin D levels may be linked to increased risk of developing COPD. In some clinical studies, lower levels of vitamin D, measured as plasma 25-hydroxyvitamin D (25(OH) D), have been associated with lower lung function and faster lung function decline, but the results are conflicting. Aim of the study: The aim of this study is to evaluate the evidence of the effect of vitamin D on COPD. Subjects and methods: The present study, included 120 subjects, 80 patients diagnosed as COPD and 40 healthy volunteers (20 smokers and 20 nonsmokers). Plasma 25-OHD was measured by Enzyme Linked Immunosorbent Assay (DiaSorin, Stillwater, Minnesota, USA) in all study participants. Results: The mean concentration of 25-OH-D was significantly higher in the reference groups (smokers and nonsmokers) compared with severe COPD group (p= 0.001, 0.001) respectively. The mean concentration of 25-OH-D was significantly higher in the reference groups (smokers and nonsmokers) compared with moderate COPD group (p= 0.029, 0.049) respectively. The mean concentration of 25-OH-D was not significantly higher in the reference groups (smokers and nonsmokers) compared with the mild COPD group. Conclusion: We observed a novel association of lower plasma 25(OH) D levels with a higher risk of COPD. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of The Egyptian Society of Chest Diseases and Tuberculosis.