Objectives: Examine the correlation of the lipid profile in sepsis with markers of acute inflammation, existing comorbidities, developed complications of sepsis and final clinical outcome. Study design: A cross-sectional study with historical data. Participants and methods: The research includes 50 patients with sepsis who were hospitalized in the Intensive Care Unit of Internal Medicine, University Hospital Centre Osijek from July 1, 2022, to February 28, 2023. The data of examinees were collected from medical documentation: the general features, existing comorbidities, developed complications, reason for hospitalization, laboratory parameters, chronic therapy and final clinical outcome. Results: The most common source of infection is the respiratory system. Patients who were mechanically ventilated had a higher mortality rate. Arterial hypertension was the most common comorbidity, and acute kidney injury was the most common complication. There is a significant negative correlation between HDL and CRP and IL-6 values. Liver lesions occur more often with higher HDL values. Patients with higher cholesterol values developed nosocomial infections more often and had a higher number of leukocytes. There is a negative association between triglycerides and atrial fibrillation. Patients who received insulin analogs had a better final clinical outcome. Conclusion: Changes in lipid metabolism and their relationship with inflammatory indicators were found in patients with sepsis. A low concentration of HDL is associated with higher values of CRP and IL-6 as a part of systemic inflammatory response. An increase in total cholesterol is proportional to the number of leukocytes, which are simultaneously indicators of the severity of inflammation. Based on the obtained results, lipoproteins may represent potential markers in the systemic inflammatory response.