Functional network topology was compared between neonates with congenital heart disease (CHD) and normal controls and sex-X-CHD interactions were investigated. Using a cost-independent analysis, CHD neonates displayed reduced segregation globally (modularity, transitivity) and nodally (clustering coefficient, participation coefficient) mainly in frontal and subcortical regions; no significant sex-X-CHD interactions were found. Using a cost-dependent analysis, CHD neonates displayed reduced integration and segregation globally (global efficiency, transitivity) and nodally (nodal efficiency, clustering coefficient) in frontal, temporal, and subcortical regions. Significant sex-X-CHD interactions (M>F) were found in similar regions. Results may support a neurophysiological basis for differential neurodevelopmental outcomes related to sex.