We describe a case of fatal acute appendicitis in a neonate associated with congenital cardiac disease requiring staged surgery. Neonatal appendicitis is extremely rare and usually associated with prematurity and congenital abdominal conditions. This report serves to highlight the risk of this disease due to vascular insufficiency and ischemia in neonates with congenital cardiac disease and highlight the importance of considering this diagnosis in such a neonate with unexplained sepsis even in the absence of clear abdominal signs.