Purpose: To assess the effect of intravenous chloride load on prognosis in intensive care unit (ICU) patients with different initial serum chloride levels. Materials and methods: Participants from the Medical Information Mart for Intensive Care IV database were di-vided into low, normal (>100 and <= 110 mEq/L), and high chloride groups according to initial chloride levels. Re-cords of intravenous fluids were extracted to calculated the volume adjusted chloride load (VACL) and VACL per body weight (VACL-W). The associations of VACL, VACL-W, and changes in serum chloride concentration (Delta Cl) with mortalities were investigated in different initial chloride groups. Results: Respectively, 4593 (20.9%), 13,364 (60.9%), and 3978 (18.1%) patients had a low, normal, and high initial chloride level. Interactions were found between initial chloride levels and VACL, VACL-W, and Delta Cl on mortality risks. In normal and high chloride groups, increased VACL, VACL-W, and Delta Cl were associated with higher ICU and hospital mortalities. However, in the low chloride group, multivariable models found no associations between VACL, VACL-W, or Delta Cl with mortalities. Conclusions: High chloride load and increased serum chloride level were associated with poor outcomes in patients with normal or high initial chloride levels, but not in those with a low initial chloride level. (c) 2022 Elsevier Inc. All rights reserved.