BACKGROUND: Pathophysiology of affective disorders (AD) remains uncertain. There is speculation around the role of purinergic neurotransmission dysfunction in major depressive disorder (MDD) and bipolar disorder (BD). Previous studies suggested lower mean uric acid (UA) levels in MDD when compared to BD. This hypothesis would allow the use of UA as a biomarker for differentiating BD from MDD in patients presenting with depressive symptoms. METHODS: This study was conducted at the Department of Psychiatry and Mental Health, CH Tondela-Viseu, Viseu, Portugal. We compared serum UA levels of inpatients with acute episodes of MDD, as well as BD in its different phases (depressive, mixed and manic). RESULTS: The sample consisted of 60 patients, after exclusion criteria were applied. Subjects with BD-manic episode showed higher levels of serum IJA compared to BD-mixed episode, BD-depressive episode and MDD patients (5.33 +/- 1.26 mg/dL vs. 4.85 +/- 1.34 vs. 4.40 +/- 1.20 vs. 4.96 +/- 0.97), but this difference did not reach statistical significance (P=0.265). Comparing BD as a single group against MDD (P=0.5277), and further subdividing the sample in BD types I and II according to DSM-5 criteria (P=0.804) produced no statistically relevant remarks. A significant difference between unipolar vs. bipolar depression could not be established (P=0.236). CONCLUSIONS: Our study did not confirm higher levels of UA in BD when compared to MDD. Although participants in mania had the highest UA serum level, the difference did not reach statistical significance. New studies are needed to clarify the purinergic dysfunction in AD.