CO₂ removal by the lungs depends upon ventilation and pulmonary blood flow, with end tidal CO₂ (EtCO₂) as surrogate for it. We studied indices based on EtCO₂ measured routinely during anesthesia for cardiac catheterization, along with simultaneously calculated Qp:Qs (pulmonary-to-systemic-blood-flow ratio) in children with complex congenital heart disease to assess the relationship between these measures. A retrospective, single-center, correlational cohort study was conducted at a tertiary-care, free-standing children’s hospital. All included subjects had Qp:Qs calculated as well as EtCO₂ and PaCO₂ documented during a single cardiac catheterization. Children with stage-1 single ventricle or complex biventricular repair with highly variable Qp:Qs were defined as Group 1, and Group 2 comprised those with stage 2 or 3 repairs with less variable Qp:Qs. Exclusion criteria were uncuffed artificial airway, EtCO₂ > PaCO₂, and abnormally high Qp:Qs. EtCO₂ indices were defined as EtCO₂:PaCO₂ (alveolar functional fraction) and EtCO₂ gap (PaCO₂–EtCO₂). Correlation coefficients were obtained between Qp:Qs and EtCO₂ indices in both groups. A total of 29 patients in Group 1 and 24 in Group 2 underwent final analysis. Even with highly variable Qp:Qs, Group 1 showed a strong correlation between Qp:Qs and EtCO₂:PaCO₂ (r = 0.83, p < 0.0001). A similarly strong correlation was maintained in Group 2 (r = 0.79, p < 0.0001) and in both groups combined (r = 0.86, p < 0.0001). A very strong negative correlation was present between Qp:Qs and EtCO₂ gap (r = − 0.77, p < 0.0001). EtCO₂:PaCO₂ has a very strong correlation with Qp:Qs simultaneously calculated during catheterization. It can be an additional parameter to estimate Qp:Qs in critical management of children with congenital heart disease. Our results also provide a basis for future prospective studies to assess dynamic changes in EtCO₂-based indices and Qp:Qs.