Vitamin D has been associated with multiple sclerosis (MS) and several markers of disease state in whites. There are limited reports of vitamin D's influence in MS in ethnic groups, such as in Hispanics. In this study, we compared vitamin D levels in Hispanics and whites with MS and tried to determine whether season or increasing disability influence hypovitaminosis D in Hispanics with MS. Serum 25-hydroxyvitamin D [25(OH)D] levels and clinical characteristics were compared in a cross-sectional sample of Hispanics (n = 80) and whites (n = 80) with MS recruited from the University of Southern California. Serum 25(OH)D levels were significantly lower in Hispanics than whites with MS (mean and standard deviation 25.1 ± 9.4 and 37.3 ± 19.8 ng/ml, respectively; p < 0.001). Hispanics were significantly more likely than whites to be vitamin D insufficient (≤ 30 ng/ml; 70 vs. 41 %, respectively; p < 0.001) and deficient (≤ 20 ng/ml; 40 vs. 14 %, respectively, p < 0.001). In Hispanics, serum 25(OH)D levels were not influenced by season (p = 0.8) or higher physical disability (EDSS ≥ 6, p = 0.7). We found that the relationship between vitamin D and MS differs by Hispanic ethnicity. Hypovitaminosis D was significantly more common among Hispanics than among whites with MS, and the majority of Hispanics were vitamin D insufficient. Interestingly, there was no association between vitamin D levels and season or increasing disability in the Hispanics. Our findings imply that factors influencing vitamin D levels and possibly vitamin D requirements may vary by ethnicity in patients with MS. These results should be confirmed in larger, prospective multi-ethnic cohort studies.