If there is no obstruction to blood flow, infants and children with this defect can be relatively asymptomatic. However, if there is obstruction anywhere along the abnormal course of the blood flow, they can be quite ill in the first hours to days of life.

Children with total anomalous pulmonary venous return present with varying degrees of cyanosis. If there is no obstruction to blood flow, infants and children with this defect have obligate mixing of saturated and de-saturated blood in the right atrium, and right-to-left shunting of partially deoxygenated blood across the atrial septal defect. However, if there is obstruction to pulmonary venous return, there may be severe cyanosis with rapid development of acidosis.

The degree of obstruction to pulmonary venous return may be mild with the supracardiac type, as there may be mild compression of the vertical vein between the left pulmonary artery and left bronchus. However, in infracardiac drainage, the anomalous pulmonary veins are always obstructed and require immediate surgical repair. Obstructed pulmonary venous return is a surgical emergency.