Background: Down Syndrome (DS) is the common genetic cause of moderate intellectual disability. DS have an increased incidence of Congenital Heart Disease (CHD), gastrointestinal anomalies, endocrine dysfunction of which thyroid dysfunction are the most common. Aim: Assessment of the changes in Thyroid Function Test (TFT) among a group of phenotypically DS children and compare it with a small group of the age-matched general population. Methods: This case-control study included measurement of TFT in a small group of children with DS who visited Al-Zahra teaching hospital for different complaints and compared to TFT in age-matched seems to be healthy children who visited the outpatient clinic of Al-Zahra teaching hospital as a control group. Results: Thirty-four children aged 5 days to 9 years with phenotypical features of DS were included in this study, 8 (23%) of them had hypothyroidism with subclinical hypothyroidism in most of them (6 children), 3 (8%) of them had hyperthyroidism and 2 (5.8%) had thyroid hormone resistance. We also found a statistically significant difference in TFT between DS children and the general population. The study also showed that Thyroid-Stimulating Hormone (TSH) level is higher and Thyroxin (T4) level is lower in DS children who had other associated anomalies like CHD compared to children without such anomalies, but it was statistically not significant. Conclusion: DS children had a high frequency of thyroid dysfunction with subclinical hypothyroidism was the common finding.