For a study, researchers sought to determine the effect of intravenous chloride load on prognosis in ICU patients with varying baseline serum chloride levels. Participants from the Medical Information Mart for Intensive Care IV database were divided into 3 groups based on their initial chloride levels: low, normal (>100 and ≤110 mEq/L), and high. The volume-adjusted chloride load (VACL) and VACL per body weight were calculated using intravenous fluid records (VACL-W). In different initial chloride groups, the associations of VACL, VACL-W, and changes in serum chloride concentration (ΔCl) with mortality were investigated. Patients with a low, normal, or high initial chloride level were 4,593 (20.9%), 13,364 (60.9%), and 3,978 (18.1%), respectively. The effects of initial chloride levels, VACL, VACL-W, and ΔCl on mortality risks were discovered. Increased VACL, VACL-W, and ΔCl in the normal and high chloride groups were associated with higher ICU and hospital mortalities. Multivariable models found no associations between VACL, VACL-W, or ΔCl and mortality in the low chloride group. High chloride load and serum chloride levels were linked to poor outcomes in patients with normal or high initial chloride levels but not those with low initial chloride levels.