Little is known about the role of a strong ions in humans with respiratory abnormalities. In this study, we investigated the associations between partial carbon dioxide pressure (pCO2) and each of sodium ion (Na+) concentrations, chloride ion (Cl−) concentrations and their difference (SIDNa-Cl). Blood gas data were obtained from patients in a teaching hospital intensive care unit between August 2013 and January 2017. The association between pCO2 and SIDNa-Cl was defined as the primary outcome. The associations between pCO2 and [Cl−], [Na+] and other strong ions were secondary outcomes. pCO2 was stratified into 10 mmHg-wide bands and treated as a categorical variable for comparison. As a result, we reviewed 115,936 blood gas data points from 3,840 different ICU stays. There were significant differences in SIDNa-Cl, [Cl−], and [Na+] among all categorized pCO2 bands. The respective pCO2 SIDNa-Cl, [Cl−], and [Na+] correlation coefficients were 0.48, −0.31, and 0.08. SIDNa-Cl increased and [Cl−] decreased with pCO2, with little relationship between pCO2 and [Na+] across subsets. In conclusion, we found relatively strong correlations between pCO2 and SIDNa-Cl in the multiple blood gas datasets examined. Correlations between pCO2 and chloride concentrations, but not sodium concentrations, were further found to be moderate in these ICU data.