Background: Sleep disordered breathing (SDB) in typically developing (TD) children is associated with adverse cardiovascular effects. As children with Down syndrome (DS) are at increased risk for SDB, we aimed to compare the cardiovascular effects of SDB in children with DS to those of TD children with and without SDB. Methods: Forty-four children with DS (3–19 years) were age and sex matched with 44 TD children without SDB (TD−) and with 44 TD children with matched severity of SDB (TD+). Power spectral density was calculated from ECG recordings, for low frequency (LF), high frequency (HF), total power and the LF/HF ratio. Results: Children with DS had lower HF power, and higher LF/HF during sleep and when awake. There were no differences between groups for LF power. SpO2 nadir, average SpO2 drop and SpO2 > 4% drop were larger in the DS group compared to the TD+ group (p < 0.05 for all). Conclusions: Our findings demonstrate significantly reduced parasympathetic activity (reduced HF power) and increased LF/HF (a measure of sympathovagal balance) in children with DS, together with greater exposure to hypoxia, suggesting SDB has a greater effect in these children that may contribute to an increased risk of adverse cardiovascular outcomes. Impact: Sleep disordered breathing in children with Down syndrome exacerbates impaired autonomic control and increases exposure to hypoxia, compared to typically developing children.In typically developing children sleep disordered breathing has adverse effects on autonomic cardiovascular control.The prevalence of sleep disordered breathing is very high in children with Down syndrome; however, studies on the effects on cardiovascular control are limited in this population.This study supports screening and early treatment of sleep disordered breathing in children with Down syndrome.