Objectives To determine the validity of using UBCO 2 G for monitoring sick children with cardiac disease. Design A prospective, observational non interventional cohort study. Setting King Abdul Aziz Medical City, Pediatric Cardiac ICU (PCICU), Riyadh. Patients Between April 2011 and May 2013, 257 patients admitted to our PCICU were recruited in the study. Intervention Arterial and central venous blood samples were collected as needed per patients' conditions. Patients' clinical and laboratory data were collected simultaneously. Results A total of 421 data sets with arterial, upper (SVC) and lower (FV) body central venous PCO 2 were collected spontaneously from 257 patients age 17.0±25.8months, weight 7.45±5.53kg. UBPCO 2 G was higher than lower (art-FV) body PCO 2 (LBPCO 2 G) gap 7.80±3.28 vs. 5.95±3.65mmHg ( p =0.001. In 75% of our data sets UBPCO 2 G was ⩽9.65 and LBPCO 2 gap was ⩽7.8mmHg. Patients with UBPCO 2 G ⩾9.65 vs. p =0.014), BUN 6.1±5.2 vs. 4.8±2.1mmol/L ( p =0.013), creatinine 48±17 vs. 43±13μmol/L ( p =0.004), glucose 8.7±4.1 vs. 7.1±3.7mmol/L ( p =0.001) and PRISM score 9±6 vs. 7±6 ( p =0.038) and lower urine output 5.2±2.8 vs. 6.1±4.3ml/kg/3h. However patients with UBPCO 2 G ⩾6 vs. p =0.018). Conclusion Upper is higher than lower body PCO 2 gap. UBPCO 2 G ⩾9.65 was associated with higher LA, BUN, creatinine, serum glucose and PRISM and lower urine output. Patients with UBPCO 2 G ⩾9.65 were sicker. UBPCO 2 G can be used as a biomarker in monitoring children with cardiac disease.