Abstract: OBJECTIVE To explore the impact of fluid accumulation index (FAI) on the first day of ICU admission on the prognosis and risk of severe acute kidney injury (AKI) in the patients with sepsis. METHODS The adult patients with sepsis who met Sepsis-3 criteria and were admitted to the ICU for the first time between 2008 and 2022 were enrolled in the study based on the MIMIC-IV (version 3.1) database. The missing data were handled by using multiple imputations. Restricted cubic spline (RCS) models were applied to examine the potential non-linear association between the first-day FAI and the 30-day mortality rate. Multivariable Cox proportional hazards models were employed to analyze the sensitivity. The 30-day mortality rates and the risk of severe AKI in the patients with different levels of fluid accumulation were assessed by means of propensity score matching (PSM). RESULTS Totally 1877 patients with sepsis were enrolled in the study. RCS analysis demonstrated a U-shaped non-linear association between the first-day FAI and the 30-day mortality rate, with the inflection points at 0.51 and 0.70, respectively. The patients were categorized into three groups: the low FAI group (<0.51, n=535), the intermediate FAI group (0.51 to 0.70, n=319), and the high FAI group (>0.70, n=1023). The patients of the high FAI group exhibited higher severity of disease, higher score of sequential organ failure assessment (SOFA), higher level of blood lactic acid, higher incidence of severe AKI, and higher proportions of patients who were treated with vasoactive agents and continuous renal replacement therapy (all P＜0.05). Kaplan-Meier survival analysis showed that the 30-day survival rate was highest in the intermediate FAI group. After the PSM, the 30-day mortality rate and risk of severe AKI were lower in the intermediate FAI group than in the low, high FAI groups (all P＜0.05). CONCLUSIONS The FAI on the first day of ICU admission demonstrates a "U"-shaped association with the 30-day mortality rate of the sepsis patients. The patients of the intermediate FAI group exhibit lower 30-day mortality rate and risk of severe AKI.