Chronic rhinosinusitis (CRS) is a prevalent disease which is characterized by chronic inflammation of the nasal mucosa and paranasal sinuses. One of the most disabling subgroups of CRS is chronic rhinosinusitis with nasal polyposis (CRSwNP), which requires further investigation regarding its pathogenesis and management. The aim of this study was to compare the circulatory Levels of 25-OHD and Vitamin D Binding Protein (VDBP) in CRSwNP patients in healthy controls. This research is an age-gender matched case-control study. All participants were recruited from the Loghman-Hakim Hospital of Shahid Beheshti University of Medical Sciences, Tehran, Iran during June 2015 to June 2016. Plasma levels of VDBP and 25-OHD were measured using the ELISA method. Forty five CRSwNP patients and forty five healthy individuals (23 females and 22 males in both groups) participated in this study. The mean plasma levels of 25-OHD were significantly lower in CRSwNP patients compared to healthy controls (36.27%, P<0.001). However, VDBP serum levels were not significantly different between CRSwNP and control groups. VDBP levels were significantly higher (P=0.017) in women (274.29 ± 72.30 μg/ml) compared to men (234.73 ± 80.04 μg/ml). However, the mean serum levels of 25- OHD were not significantly different between men and women. CRSwNP patients have significantly lower serum levels of 25-OHD compared to healthy individuals, however, VDBP levels were not different between the CRSwNP and healthy individuals.