OBJECTIVE: Type 2 diabetes mellitus (T2D) is characterized by the dysregulation of innate immunity leading to higher rates of Staphylococcus aureus nasal carriage, an important risk factor for severe infections. 25-hydroxy vitamin D (25(OH) D) may contribute, via the production of the antimicrobial peptide cathelicidin (LL-37), to epithelial host defense against S. aureus. This study evaluated whether 25(OH)D and LL-37 levels determine S. aureus nasal carriage. METHODS: Two consecutive nasal swabs were obtained from 118 T2D patients to determine S. aureus nasal carriage status. Serum levels of 25(OH)D and LL-37 were measured using chemiluminescence immunoassay and enzyme-linked immunosorbent assay, respectively. Supplementation of vitamin D by a number of participants was taken into account and evaluated. RESULTS: Forty-two T2D patients (35.6%) were found to be colonized by S. aureus. Vitamin D deficiency was detected in sixty-nine patients (65.7%). Median value for LL-37 in T2D patients was 0.89 ng/ml (range 0.05-8.62 ng/ml). Circulating levels of LL-37 were higher in nasal carriers compared to non-carriers (1.25 ng/ml vs 0.72 ng/ml; p < 0.001). No difference was found in serum 25(OH) D levels between carriers and non-carriers. 25(OH)D and LL37 serum levels correlated positively in non-carriers, while the relationship was inversed in the carrier group. Vitamin D supplementation was not associated with lower incidence of S. aureus nasal carriage (p = 0.706). CONCLUSIONS: T2D patients presented decreased serum levels of 25(OH)D and LL-37, indicating a potential impairment of innate immunity. Expression of LL-37 may be induced by S. aureus nasal carriage among people with diabetes. Vitamin D supplementation did not influence S. aureus nasal colonization in T2D patients.