Background. To address the cause(s) of the significant differences in chloride (Cl(-)) concentrations between point-of-care blood gas analyzers and central laboratory analyzers. Methods. Cl(-) concentrations measured simultaneously by a blood gas analyzer (ABL800 FLEX) and a central laboratory analyzer (Hitachi7600) were collected in patients with severe acidemia (pH < 7.20) (n = 32) and were examined for correlations between differences in Cl(-) and factors associated with the acid-base status. Cl(-) concentrations were measured with both analyzers for samples with different concentrations of lactate, inorganic phosphate, or bicarbonate (HCO(3) (   -)). Results. The differences in Cl(-) concentrations were correlated with HCO(3) (   -) concentrations (r = 0.72, P < 0.0001) and anion gap (r = 0.69, P < 0.0001). Only the addition of HCO(3) (   -) proportionately increased Cl(-) levels measured by a Hitachi7600, but it did not affect those measured by an ABL800FLEX. Conclusion. Cl(-) measurements with some analyzers may be influenced by HCO(3) (   -) concentrations, which could result in the observed discrepancies.