Background: Evidence indicates that the serum concentration of uric acid (UA) in patients may relate both to the pathophysiology and therapeutics of bipolar disorder (BPD). The purpose of this study was to examine the changes and clinical significance of serum UA concentrations in first-episode manic patients suffering from BPD. Methods: Seventy-six drug-naive patients with first-episode bipolar mania and 76 age-and gender-matched healthy subjects were recruited. Young Mania Rating Scale and Hamilton Depression Rating Scale were used to assess clinical symptoms. We tested serum UA concentrations by sandwich enzyme-linked immunosorbent assay at baseline and at the end of 8-week treatment in BPD patients and in the control group. Results: After 8-week quetiapine and sodium valproate treatment, this study revealed that the serum UA concentrations in remitted patients were significantly lower than nonremitted patients; however, those remitted patients still had higher serum UA than healthy controls. We discovered that the baseline UA concentration was higher in nonremitted than remitted patients after 8 weeks of treatment. Finally, a positive association was found between serum UA and symptom relief in the first episode of manic disorder patients. Conclusion: Patients with first-episode BPD had high levels of serum UA, which responds to treatment mainly in remitted patients. Our results suggest that serum UA concentrations might present potentially a trait marker in bipolar patients.