Background <p>Sepsis in patients with liver cirrhosis is associated with poor outcomes. Early prognostic stratification is crucial for guiding clinical decisions. We investigated the relationship between serum chloride levels and mortality in septic patients with liver cirrhosis.</p> Methods <p>Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 3.0) database. We used multivariable Cox regression models and restricted cubic spline analysis to assess the association with serum chloride levels and 30-day, 60-day and 365-day all-cause mortality.</p> Results <p>2778 septic patients with liver cirrhosis were included and 827 (29.77%) patients died within 30 days. Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile (<i>P</i> &lt; 0.05). Kaplan-Meier analysis showed higher mortality rates in the low serum chloride group (<i>P</i> &lt; 0.001). Restricted cubic spline analysis revealed an L-shaped relationship between serum chloride and mortality at 30, 60, and 365 days (all P-overall &lt; 0.001), with a clear inflection point at 102.5 mmol/L. Below this threshold, mortality risk decreased steeply, whereas above it the risk remained relatively stable.</p> Conclusions <p>Serum chloride levels were independently associated with mortality in septic patients with liver cirrhosis in an L-shaped manner, with a critical threshold identified at 102.5 mmol/L. This cut-off may provide clinically meaningful guidance for risk stratification in this high-risk population.</p> Clinical trial number <p>Not applicable.</p>