Background: Sepsis is a state of augmented oxidativestress and diminished antioxidant capacity. High den- sity lipoprotein (HDL) particles were shown to possessantioxidant and anti-inflammatory properties, as wellas Paraoxonase 1 (PON1), which is an enzyme that isalso protective against HDL oxidation. Previous stud- ies suggested a possible role of decreased PON1 activ- ity or HDL levels in sepsis patients. Aims: The present study was designed to test a hypoth- esis that higher PON1 activity and HDL-cholesterollevels could predict a better survival in sepsis patients. Study Design: Observational study. Methods: Venous blood samples were collected fromsepsis patients for HDL-cholesterol levels, PON1 ac- tivity and cytokine assays (TNF-&#945; and IL-6) and AcutePhysiologic and Chronic Health Evaluation II (APACHEII) scores were calculated in order to weight patientsdisease severity on the day of sepsis diagnosis. Patientswere followed-up until the 28th day for any cause intra- hospital mortality. Data were statistically analyzed foreffects of study parameters on patients survival. Results: In total, 85 patients with sepsis were includedin the study. The mean age was 65.2±17.9 years and48 were male; at the end of the 28-day follow-up pe- riod, 46 survived. TNF-&#945; (86.9±10.5 vs 118.6±16.4)and IL-6 levels (906.7±82.7 vs 1323.1±54.3) were sig-nificantly higher in non-survivors, while PON1 activity(140.7±42.3 vs 66.7±46.6) and HDL-cholesterol lev-els (43.6±8.1 vs 34.5±8.9) were significantly higher insurvivors (p<0.001 for all). TNF-&#945; (r=-0.763) and IL-6levels (r=-0.947) showed strong negative correlations,PON1 activity (r=0.644) and HDL-cholesterol levels(r=0.477) showed positive correlations with patient sur-vival (p<0.001 for all). Survival estimates significantlyfavored TNF-&#945; (Log Rank 59.5, p<0.001) and IL-6levels (Log Rank 53.2, p<0.001) according to PON1activity (Log Rank 5.4, p<0.03) and HDL-cholesterollevels (Log Rank 8.3, p<0.005). Regression analysesfor relative contributions of parameters to survivalshowed that higher IL-6 levels (t:-16.489, p<0.001)were the most significant negative factor for survival,and TNF-&#945; levels (t:-4.417, p<0.001), whereas PON1activity had a positive effect (t:3.210, p<0.003).Conclusion: The present study showed that althoughlow PON1 activity and HDL-cholesterol levels wererelated to mortality, higher levels were not found to beas predictive as cytokine levels for survival.