Background: Although uric acid (UA) is one of the most important antioxidants in plasma and appears to be neuroprotective in animal models, results from human studies are controversial. In this study, we investigated the kinetics of serum UA concentrations in the acute, subacute and chronic phase of ischemic stroke and its relation with initial stroke severity, stroke evolution in the subacute phase and long-term stroke outcome. Methods: Serum concentrations of UA were measured in 199 stroke patients at admission (median, 2.8 h after stroke onset), at 24 h, 72 h, day 7, month 1 and month 3 after onset of stroke. We evaluated the relationship between changes in UA concentrations and (a) stroke severity [patients with transient ischemic attack (TIA) vs. stroke patients, National Institutes of Health Stroke Scale (NIHSS) score at admission], (b) stroke evolution (stroke progression, infarct volume at 72 h), and (c) stroke outcome [modified Rankin scale (mRS) score at month 3, mortality]. Results: UA concentrations decreased significantly during the first 7 days after stroke onset before returning to baseline (p<0.001). Mean plasma UA concentrations decreased from 336.66±113.01 μmol/L at admission to 300.37±110.04 μmol/L at day 7 (p<0.001) in patients with stroke, but did not change significantly in patients with TIA. Changes in UA concentrations from admission to day 7 (ΔUA day 7 ) correlated with the NIHSS score (ρ=0.32; p<0.001), stroke progression (ρ=0.29; p=0.001), infarct volume (ρ=0.37; p<0.001), mRS score (ρ=0.28; p=0.001) and mortality (p=0.010). Conclusions: Decreases in UA during the first week after onset of stroke correlates with more severe stroke, unfavorable stroke evolution, and poor long-term stroke outcome. Clin Chem Lab Med 2010;48:383–90.