To date it is unknown if there is a predisposition to sepsis. In this respect, genetic studies have been conducted with the aim to find gene variants which can point out a higher predisposition to developing sepsis. The primary objective of this study is to highlight whether the genetic polymorphism of Angiopoietin-2 gene (ANG2-35G>C) is present mainly in septic patients. As secondary objectives we aimed to evaluate if there are any associations between ANG2-35G>C polymorphism and the severity scores Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score (SAPS) as well as routine tests in septic patients such as C reactive protein (CRP), procalcitonin (PCT). We enrolled adult patients admitted to the Intensive Care Unit (ICU). After admission to the ICU and the diagnosis of sepsis, blood samples were collected and the severity scores: APACHE II, SAPS were calculated on the first day of ICU admission. We recorded the following from the blood samples: CRP, PCT, angiopoietine2 (Ang-2). We performed several one-way ANOVA tests to determine any significant mean difference of the analyzed variables. We observed that variant genotypes of ANG2-35G>C gene polymorphism are significantly related to CRP, aspect which increases this biomarker credibility compared with others (i.e., PCT), in septic patients. ANG2-35G>C gene polymorphism is associated with severity scores, APACHE II, and SAPS in sepsis.