Infants with Congenital Heart Disease (CHD) are at high risk of neurodevelopmental disorders. We acquired presurgical neonatal T2-weighted MRI (N=66), cerebral oxygen delivery (CDO2; N=53), and 22-month cognitive and motor scores (N=44). Atypicality indices, representing the degree of deviation of a regional brain volume from the normative neonatal mean for a given gestational age, sex and postnatal age, were calculated. Reduced CDO2 was indirectly associated with lower cognitive scores through the mediating effect of negative bilateral caudate and thalami atypicality indices. The aetiology of cognitive impairments in CHD may encompass poor CDO2 leading to impaired caudate and thalamus growth.