Introduction Vitamin D is known to have immunomodulatory functions and has action on chronic inflammatory processes, such as nasal polyposis. Objective The present study assessed the levels of 25-hydroxy vitamin D and high-sensitivity C-reactive protein (hs-CRP) in patients with nasal polyposis, as compared with healthy control subjects, and identified their association with disease severity in nasal polyposis. It further assessed the levels of 25-hydroxyl vitamin D and hs-CRP in patients with nasal polyposis and atopy and compared it with patients with nasal polyposis without atopy. Methods This was a cross-sectional study involving 2 groups: 80 patients with nasal polyposis and 80 healthy subjects. In patients with nasal polyposis, the disease severity is assessed by the sino-nasal outcome test (SNOT20) and by the Lund & Mackay staging system. Levels of 25-hydroxy vitamin D and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA). Result The mean 25-hydroxyl vitamin D levels (ng/ml) was 12.01 ± 7.29 for cases and 22.87 ± 14.95 for controls, with p < 0.0001. The mean hs-CRP levels (mg/L) was 5.99 ± 2.74 in cases and 2.41 ± 1.95 in controls, with p < 0.0001. The severity of polyposis correlated negatively with serum levels of 25-hydroxy vitamin D and positively with hs-CRP. Conclusion The study has thus shown significant correlation between vitamin D deficiency and inflammation in patients with nasal polyps.