Background/aim: Calculation of the chloride:sodium (Cl-:Na+) ratio is proposed to enable a quick evaluation of the effect of Cl- and Na+ on the acid-base balance in critically ill patients. In the present study, the relationship of the Cl-:Na+ ratio of septic patients with acidbase status and ICU mortality were investigated. Materials and methods: In our two-center study, 434 patients who were diagnosed with sepsis were included. The patients were divided into three groups: low (<0.75), normal (≥0.75, <0.80), and high (≥0.80) Cl-:Na+ ratio groups. Patients' demographic data, blood gas values, length of ICU stay, and ICU mortality were recorded. Results: In the low and high groups, ICU mortality was significantly higher than in the normal group (29.3%, 37.1%) (P = 0.005). There was a negative correlation between the Cl:Na+ ratio and each of HCO3 -, standard base excess, and PaCO2 (r2 = 0.21, r2 = 0.19, and r2 = 0.17) (P < 0.001 for each). In the multivariate analysis, the ICU mortality was increased 2.6-fold (1.2-5.8) by low Cl-:Na+ ratio (P = 0.019). Conclusion: The Cl-:Na+ ratio is a useful parameter for showing the relationship between Cl- and Na+ and their impact on acid-base status. Low Cl-:Na+ ratio at ICU admission can be used as a prognostic indicator for increased ICU mortality in septic patients.