The study describes the link between serum levels of surfactant protein D, its genetic polymorphisms and risk of Chronic Obstructive Pulmonary Disease. Single nucleotide polymorphisms has been genotyped using PCR and restriction analysis. Serum SP-D levels were measured using a specific immunoassay. Autoantibodies including anti dsDNA, antinuclear and antinucleosome antibodies levels were also recorded. It was found that allele ‘A’ at rs3088308 (p=0.000, B=-0.399) and ‘C’ allele at rs721917 (p=0.021; B=-0.344) were associated with significantly low serum SP-D levels. Additionally allele ‘T’ at rs721917 was significantly associated with risk of COPD (p=0.042). Haplotype ‘A C’ (A in rs3088308 and C in rs721917) was under-represented in cases as compared to controls (p=0.005). The results showed that exacerbation status is a significant determinant of serum SP-D even after adjusting for genetic factors. This study reports for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirms the association of rs721917 with risk of COPD and serum SP-D levels. In addition, the protective effect of haplotype ‘A C’ against COPD was also revealed.