Several findings suggest lower levels of serum uric acid in multiple sclerosis (MS) patients. The aim of this study is to investigate relationships of uric acid serum levels in relapse–remitting (RR) MS patients with clinical activity of disease and blood–brain barrier (BBB) condition. Sixty-three definite RRMS patients and 40 controls divided into two groups: 20 healthy donors and 20 patients with other inflammatory neurological diseases (OINDs) were analysed. By using a quantitative enzymatic assay according to the manufacture's protocol and a commercial uric acid standard solution, serum uric acid levels were measured and the results were standardized. To investigate BBB function, magnetic resonance imaging after administration of gadolinium was used. MS patients were found to have significantly lower serum uric acid levels (193.89 ± 49.05 μmol/l; mean value ±SD) in comparison with healthy donors (292.7 ± 58.65 μmol/l; P=0.000) and OIND patients (242.7 ± 46.66 μmol/l; P=0.001). We found that MS patients with relapse had significantly lower serum uric acid levels (161.49 ± 23.61 μmol/l) than MS patients with remission (234.39 ± 41.96 μmol/l; P=0.000) and more over, MS patients with BBB disruption had significantly lower serum uric acid levels (163.95 ± 26.07 μmol/l) than those with normal BBB (252.48 ± 25.94 μmol/l; P=0.000). Further, we also found that serum uric acid level independently correlated with disease activity, BBB disruption, and gender. These results indicate that lower uric acid levels in MS patients are associated with relapse and suggest that uric acid might be beneficial in the treatment of MS.