OBJECTIVE End tidal carbon dioxide (EtCO2) monitoring is considered to reflect real-time estimation of partial pressure of carbon dioxide in arterial blood (PaCO2) noninvasively. However, knowledge about its relationship with PaCO2 in critically ill pediatric and neonatal patients is limited. The primary objective was to evaluate predictive capability of end tidal carbon dioxide monitoring and secondary objective was to determine the influence of severity of lung disease on EtCO2 and PaCO2 relationship. METHODS This was a prospective, nonrandomized, consecutive enrollment study carried out in neonatal and pediatric intensive care units of a tertiary care children hospital. It was conducted in 66 neonates and 35 children receiving mechanical ventilation. Severity of lung disease was estimated by ventilation index and PaO2/FiO2 (P/F) ratio. Simultaneous recording of EtCO2 and PaCO2 levels was done and data were analyzed for correlation and agreement. RESULTS In neonates, 150 EtCO2 and PaCO2 pairs were recorded. The mean weight ± SD of patients was 2.1 ± 0.63 kg. PaCO2 had a positive correlation with EtCO2 (r = 0.836, 95% CI = 0.78-0.88). P/F ratio <200 adversely affected relationship. In infants and children, 96 pairs were recorded. Mean age ± SD of patients was 4.20 ± 4.92 years and mean weight ± SD was 13.1 ± 9.49 kg. PaCO2 had an excellent correlation with EtCO2 (r = 0.914, 95% CI = 0.87 and 0.94). P/F ratio <200 adversely affected relationship. CONCLUSIONS EtCO2 monitoring displayed a good validity to predict PaCO2. Correlation was affected by low P/F ratio (<200); hence, it is recommended that blood gases be measured in these patients until such time that a good relation can be established between end tidal and arterial CO2 values.