Background <p>Sepsis-associated liver injury (SALI) has a high mortality rate, but there is no established prognostic criterion for its outcomes. Although serum phosphate levels have been associated with mortality in several critical illnesses, research on their relationship with SALI is limited. This research aimed to explore the association between serum phosphate levels and 28-day mortality in SALI patients.</p> Methods <p>We enrolled patients with SALI from the Medical Information Mart for Intensive Care-IV database. Serum phosphate levels were recorded within the initial 24&#xa0;h of Intensive Care Unit admission. The primary outcome of interest was 28-day mortality. Multivariable Cox regression was applied to examine the association between serum phosphate and mortality. Additional subgroup analyses were carried out to ensure these findings.</p> Results <p>We analyzed data from 538 SALI patients, with a mean age of 69 years, of 61.9% male. The 28-day mortality rate was 35.1%. In the unadjusted analysis, higher phosphate levels at admission were significantly linked to increased 28-day mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.18 to 1.29; <i>p</i> &lt; 0.001). After controlling for covariates such as age, sex, race, laboratory results, comorbidities, and illness severity, the association remained significant (HR, 1.13; 95% CI, 1.04 to1.22; <i>p</i> = 0.006). Subgroup confirmed the consistency of these findings.</p> Conclusion <p>Higher serum phosphate levels at admission were independently linked to increased 28-day mortality in SALI patients. This suggests that serum phosphate could be a useful prognostic marker for risk stratification and clinical management in SALI.</p> Clinical trial number <p>Not applicable.</p>