This study examines the predictive significance of blood High-Density Lipoprotein Cholesterol (HDL-C) levels in patients with sepsis. The study measures HDL-C levels upon admission and on the fifth day of hospitalization. The study has a cohort of 50 patients who were diagnosed based on the Sepsis-3 standards. The research was conducted at Silchar Medical College and Hospital. The results indicate that there is a notable reduction in HDL-C levels that is associated with a higher risk of death, as seen by the elevated Sequential Organ Failure Assessment (SOFA) scores in patients who did not survive. These findings indicate that serum HDL-C may be a cost-efficient and readily quantifiable biomarker to predict outcomes in sepsis. This might potentially be used as a tool for early prognostic assessment and making treatment decisions. The study emphasizes the necessity of more research to confirm these findings and investigate the mechanisms that cause the observed alterations in HDL-C levels throughout sepsis.