Down syndrome (DS) is the most common autosomal aberration among liveborns in developed and developing countries. There are several clinical features and metabolic disturbance with this syndrome. Defective oxidative balance is one of the most common metabolic problems in DS. It is suggested clinical features and metabolic disturbance specially oxidative stress in DS are a consequence of specific chromosome 21 segments, but results of many studies haven't confirmed it. Findings of recent researches have propounded mitochondrial dysfunction as causes of pathology and aetiology of DS. Defect in respiratory enzymes and mutation in mtDNA can cause mitochondrial dysfunction. Increasing in generation of reactive oxygen species (ROS) is one of the results of mitochondrial dysfunction in DS.