Sepsis still represents a syndrome with a high mortality. A timely sepsis diagnosis and an early intervention are crucial for the disease outcomes. Sepsis-associated acute kidney injury (SA-AKI) is highly prevalent but often diagnosed late. We aimed to investigate whether serum interleukin-6 (IL-6) and leukocyte cell population data (CPD) could be adequate biomarkers for the prediction of survival and SA-AKI development. We conducted a prospective observational study in a medical intensive care unit of a tertiary hospital centre in Zagreb, Croatia from June 2020 to October 2023. Adult patients with newly diagnosed sepsis were included and classified as immunocompetent or immunocompromised. Blood samples were collected upon admission. A total of 150 patients were included in the study. Ninety-six (64%) patients were immunocompetent and fifty-four (36%) were immunocompromised. The median SOFA score was 8 (6-11). SA-AKI was diagnosed in 108 (72%) patients. ICU and hospital mortality was 27.3% and 37.3%, with no significant difference between groups. Significantly higher serum IL-6 levels were noted in the immunocompromised group, while neutrophil granularity intensity was higher in the immunocompetent group. According to logistic regression analyses, elevated IL-6 levels predicted a lethal ICU outcome, while elevated IL-6 levels and neutrophil reactivity intensity were predictors of SA-AKI development. A cluster analysis revealed two patient groups with different IL-6 concentrations, and further studies indicated that the group with higher IL-6 values had significantly higher SA-AKI occurrence and increased lethal outcomes. An early serum IL-6 measurement regardless of the patients' immune status indicates disease severity. Its measurement in the early phase of disease presentation, potentially in the emergency department, might facilitate ICU admission. Further research is warranted in the field of leukocyte CDP application.