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Purpose The impact of Down syndrome on myocardial performance measured using deformation imaging and pulmonary hypertension (PH) in the neonatal period requires exploration. We aimed to assess PH and measure left (LV) and right (RV) ventricular function using deformation imaging in neonates with DS (without structural heart disease) over 5 days of age. Methods Echocardiograms were performed on Days 1, 2 and 5 to measure LV and RV dimensions, LV basal longitudinal strain (LV BLS) and systolic strain rate (LV SR), RV free wall basal longitudinal strain (RV BLS) and systolic SR (RV SR), and LV rotational mechanics. PH was assessed by examining ductal (PDA’s) shunting and tricuspid regurgitation (to estimate RV systolic pressure, RVSp). Values were compared with healthy controls. Results 17 infants with DS with a mean ±SD gestation and birthweight of 38.4±2.1 weeks and 3.1±0.5 Kg respectively were compared with 16 controls (38.3±2.0 weeks and 3.3±0.5 Kg). On Day 1, infants with DS had a higher proportion of bidirectional PDAs (100% vs. 20%, p Conclusion Infants with DS demonstrate elevated pulmonary pressures during the early neonatal period translating into lower RV function measured using deformation imaging. They also demonstrate impaired twist driven by reduced basal rotation. The clinical implications warrant further study.