Sepsis continues to be a major global health concern, characterized by high morbidity and mortality rates. As a clinical syndrome characterized by a dysregulated systemic response to infection, its progression toward life-threatening organ dysfunction is driven by an array of signaling molecules. Extracorporeal therapy has emerged as a key adjunctive strategy for the targeted elimination of these inflammatory mediators. While current modalities-including non-selective cytokine adsorption, selective lipopolysaccharides LPS adsorption, and therapeutic plasma exchange (TPE)-have shown clinical benefits in specific patient cohorts, research into more precise interventions continues.A new frontier focuses on the extracorporeal removal of cell-free DNA (cfDNA) and neutrophil extracellular traps (NETs), which are recognized as pivotal drivers of systemic inflammation. This study evaluates the Nucleocor plasma adsorption column, a pioneering device designed for the selective removal of DNA-containing structures. By targeting septic shock patients with prognostically unfavorable cfDNA elevations, this research aims to establish standardized protocols and generate the evidence base necessary for integrating this novel therapy into national clinical guidelines.