PURPOSE: Given that vitamin D (25(OH)D) contributes to immune defense, we sought to determine if deficiency of 25(OH)D was significantly associated with methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: All patients with 25(OH)D determinations at the Atlanta VAMC from 2007 to 2010 were included in the analyses. These patients were cross-referenced with a prospectively collected MRSA infection database at the AVAMC (2006-2010). Patients with one or more MRSA infections during the study period were considered MRSA-infected patients. Multivariate logistic regression was used to determine the association between 25(OH)D status [deficient (<20 ng/mL) vs. non-deficient (≥20 ng/mL)] and MRSA infection. RESULTS: A total of 6405 patients with 25(OH)D determinations were included in the analyses, of which 401 (6.3 %) were MRSA-infected patients. Mean (SD) vitamin D levels, in ng/mL, were 21.1 (12.4) and 24.0 (12.6) for MRSA-infected patients and non-MRSA infected patients, respectively (p < 0.0001). The multivariate logistic regression model confirmed associations between MRSA infection and sex, race, BMI, HIV status, and 25(OH)D [odds ratio for 25(OH)D: 1.94; 95 % confidence interval: 1.51-2.49]. CONCLUSION: MRSA-infected patients had significantly lower serum vitamin D levels than non-MRSA infected patients, even when controlling for potential confounding variables.