We evaluated how Paco2 and respiratory variables relate during and after exercise and derived a new noninvasive estimation of Paco2 in children and postoperative patients with congenital heart disease. We randomly selected 8 subjects from each of three categorized groups from our previous studies: 15 control subjects (8 to 21 years old), 16 Fontan procedure patients (9 to 22 years old), and 13 patients after right ventricular outflow tract reconstruction (RVOTR) [7 to 21 years old], and used their respiratory variables during exercise testing to estimate Paco2 (study 1). In a stepwise multiple regression analysis, end-tidal carbon dioxide tension (Petco2), age, ventilatory equivalent for carbon dioxide (minute ventilation [V̇e]/carbon dioxide production [V̇co2]), and gas exchange ratio (R) were major determinants of Paco2 in control subjects: Paco2 = 12.0 + 0.54 Petco2 + 0.15 V̇e/V̇co2 − 3.6 R + 0.22 age (r = 0.86). In addition to Petco2 and V̇e/V̇co2, arterial oxygen saturation and tidal volume were additional major determinants for Fontan procedure and RVOTR patients, respectively. We derived equations to predict the Paco2 (r = 0.92 for Fontan procedure and r = 0.74 for RVOTR). These equations were applied to the remaining study subjects to estimate Paco2 (study 2). Estimated values correlated with the measured Paco2 (r = 0.71 to 0.86), and the mean differences for the control subjects, Fontan procedure, and RVOTR patients were − 0.1, − 0.1, and – 1.0, with limits of agreement of ± 3.3, ± 4.4, and ± 3.1, respectively. Although estimated Paco2 based on the Jones equation correlated with the measured Paco2 in all groups, their slopes were significantly flatter than ours. Paco2 throughout exercise testing may be estimated in control children and postoperative pediatric patients. The Jones equation should be applied with great care in pediatric subjects.