Background: Down syndrome (DS) is the most common chromosomal abnormality. Children with DS have elevated serum uric acid (UA) levels. Objective(s): The aim of the present study was to estimate the serum UA levels in children with DS and compare it with the levels in normal children. Methods: A case control study was conducted on 200 children at Alexandria University hospital, divided into two groups. Group I: included 100 children with DS (cases). Group II: included 100 healthy children as a control group. Children of both groups were subjected to history taking, clinical examination, renal function tests and serum UA estimation. Results: 5% of patients had upper normal, 16% had high serum UA levels. None of the children in the control group had upper normal or high serum UA levels. This was statistically significant. Mean serum UA in patients was significantly higher than in the control children. There was a statistically significant positive correlation between serum UA and patients' age. No statistically significant correlation between serum UA and gender was detected in both groups. Conclusion: Serum UA was significantly higher in children with DS than in controls. There was a significant positive correlation between serum UA and patients' age.