Severe trauma associated with later disability and mortality still constitutes a major health and socioeconomic problem throughout the world. While primary morbidity and mortality are mostly related to initial injuries and early complications, secondary lethality is strongly linked to the development of systemic inflammatory response syndrome, sepsis, and ultimately multiple organ dysfunction syndrome. We herein report on a 49-year-old male patient who was admitted to the hospital after a traumatic amputation of his right forearm that was cut off while working on a landfill. After initial treatment for shock, he received immediate replantation and was transferred to the ICU. Due to the anticipated risk of a complex infection, continuous renal replacement therapy in combination with CytoSorb was initiated. During the course of the combined treatment, a rapid improvement in hemodynamics was noticed, as well as a significant reduction of IL-6 and lactate levels. Despite a recurring septic episode and the necessity for amputation, the patient clinically stabilized and underwent complete recovery. The early treatment with a combination of CVVHDF and CytoSorb was accompanied by an attenuation of the systemic inflammatory reaction, which subsided without major or permanent organ damage, despite the impressive pathogen spectrum and the pronounced local damage.