BackgroundChildren with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se’s role in AITD in Indonesian children with DS.MethodsThis cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann–Whitney, and Spearman’s rank correlation (rs). All results withp<0.05 were considered statistically significant.ResultsAmong 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 andp=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (rs=−0.439 withp=1×10-5andrs=−0.396 withp=0.001, respectively) and Tg-Ab (rs=−0.474 withp=1×10-5andrs=−0.410 withp=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (rs=-0.252,p=0.048) in the AITD group.ConclusionSelenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.