Objective: Low vitamin D levels had been shown to play a role in the pathogenesis of multiple sclerosis (MS). Currently, there is little information regarding the correlation between levels of vitamin D and MS in Chinese. This study aimed at detection of association between serum 25-hydroxyvitamin D [25(OH) D] concentrations and MS and its relation to the disease severity in Chinese. Methods: The present study was a case-control type, it included 141 patients with definitive MS on the basis of 'McDonald' criteria and 282 age-sex matched controls. All patients were clinically evaluated including disease severity using expanded disability status scale (EDSS) score and progression index (PI). Serum 25(OH) D measurements were performed at baseline. Results: The median serum level of 25(OH) D in patients with MS was 15.9 (IQR, 11.4-24.4) ng/mL, which was significantly lower (P < 0.0001) than those in healthy controls (20.6 [IQR, 15.3-27.7] ng/mL). There was a negative correlation between levels of 25(OH) D and the EDSS score (r = -0.549, P < 0.0001). In multivariate conditional logistic analyses using dichotomous 25(OH) D levels, values less than or equal to 20 ng/mL indicted higher risk of MS (OR 1.691, 95 CI: 1.058-2.394: P = 0.024). Similarly, in binary logistic multivariate analyses using dichotomous 25(OH) D levels, values less than or equal to 20 ng/mL indicted the MS high progression (OR 6.278,95 CI: 2.662-15.659; P < 0.001). Conclusion: Low serum 25(OH) D levels were associated with increased activity and progression in Chinese patients with MS. Further analytical work is required to establish a causal association between vitamin D status and MS risk and progression. (C) 2016 Elsevier B.V. All rights reserved.