Objective To study oxygen carrying capacity of red blood cell in children with congenital left-to-right shunt (CLRS) and discuss its clinical significance. Methods A total of 62 children with CLRS were selected as a trial group and 40 healthy children who had accepted clinical physical examination as a control group. ELISA test was applied to determine 2,3 -DPG content of red blood cells. At the same time, pH, PaO2, PaCO2, Hb, P50O2 and relevant outcomes were tested for correlation analysis. Results Red blood cell 2,3-DPG (2.76±0.98 μmol/mL) was higher than that of the control group. PaO2, pH, Hb were lower than those of the control group with significant differences. Among the types of CLRS, 2,3 -DPG of ventricular septal defect was the highest and that of patent ductus arteriosus ranked the second, the two of which had a significant difference (P=0.007). As for red blood cell of children with congenital heart diseases, there was linear correlation between 2,3- DPG and PaO2 as [2,3-DPG=12.007 8– (0.154 7×PaO2)], as well as between P50O2 and 2,3 -DPG as [P50O2=26.303 6+ (1.799 2×2,3-DPG)]. Conclusion Children with congenital left-to-right shunt tend to have low oxygen. Therefore, it is important to detect 2,3-DPG of red blood cell, blood gas analysis, and hemoglobin level change, in order to well understand the mechanism of congenital heart disease as well as to guide clinical practice.