BACKGROUND: Currently vitamin D3 (VD3) or cholecalciferol is considered an immunomodulator that may be implicated in nasal polyposis (NP) pathophysiology.OBJECTIVES: This study aimed to investigate if deficiency of VD3 is associated with the presence of NP in patients with cystic fibrosis (CF) and patients with chronic rhinosinusitis (CRS).METHODS: In total, 152 adult participants were included in five phenotypic groups: CF with NP (CFwNP) (n = 27), CF without NP (CFsNP) (n = 31), CRS with NP (CRSwNP) (n = 32), CRS without NP (CRSsNP) (n = 30), and controls (n = 32). The serum levels of 25(OH)-VD3 < 20 ng/mL are considered as a deficiency, 21-29 ng/mL as insufficiency, and >30 ng/mL as sufficiency. Endoscopic and imaging staging of the mucosal disease performed with the Lund-Kennedy (LK) and Lund-Mackay (LM) scoring systems, respectively. The genotype of the patients with CF and the nasal microbial colonization of the patients with CF and patients with CRS were also recorded.RESULTS: The patients with CFwNP had the lowest percentage of sufficiency in VD3 and the highest percentage in insufficiency among all the groups. The LM imaging scores were inversely correlated with the VD3 levels in both arms of the study (CF and CRS). Moreover, the LK endoscopic scores had a similar correlation in the CF groups; however, this was not the case with the CRS groups. The genotype of the patients with CF was not correlated with the VD3 serum levels. The patients with positive microbial colonization (mainly Pseudomonas and Staphylococcus aureus) had significantly lower VD3 serum levels in both the CF and CRS process.CONCLUSION: VD3 deficiency seemed to be associated with the presence of nasal polyps in the patients with CRS and in the patients with CF in a similar manner. The lower the level of serum VD3, the more severe the mucosal disease was found in the imaging studies and the more frequent microbial colonization of the patients with CF and the patients with CRS.