In this prospective single‐centre pilot observational study with patients undergoing CPB for correction of ASD or tissue mitral valve replacement, there was no difference in the classical or alternative pathways activation markers immediately following the administration of UFH but a significant rise in these markers (C3a, C5a sC5b‐9 and Bb fragment) during CPB, with gradual reduction in the level over 12–24 h post‐CPB. This evidence concerns the gene C3 and atrial septal defect.