INTRODUCTION: Septic shock is the most serious complication in intensive care that associates with significant mortality. Extracorporeal hemocorrection may improve treatment of patients with septic shock. OBJECTIVE: Evaluation of the effect of hemocorrection with the multimodal adsorbent device Efferon LPS on the dynamics of organ dysfunction and inflammation markers in patients with septic shock. MATERIALS AND METHODS: A multicenter randomized controlled study was conducted in four clinical organizations in the city of Moscow from March 2021 to May 2022. The study included 58 patients (29 men and 29 women) with septic shock. Randomization was performed in a ratio of 2:1 (hemoperfusion: control). Within 24 hours of enrollment in the study, selective hemoperfusion procedures were performed or standard therapy was used. Hemosorption using Efferon LPS was performed twice, with an interval of 24.5 (23.3–26.0) hours. RESULTS: The use of the multimodal selective hemosorbent Efferon LPS significantly reduced the severity of multiple organ failure (MOF) in patients with septic shock from 7 to 3 points on the SOFA scale after 72 hours by improving hemodynamics, respiratory and renal function. In contrast to the control group, in the Efferon LPS group, the levels of CRP, PCT and IL-6 significantly decreased in 72 hours. The severity of MOF significantly correlated with the level of CRP and PCT (Spearman’s r = 0.346 and r = 0.444, respectively). The duration of hospitalization in survived patients was 16.1 days and 30.1 days in the Efferon LPS and control group, respectively (p = 0.032). The need for a renal replacement therapy (RRT) in survivors by the 3rd day was significantly reduced only in the Efferon LPS group — from 73.7 to 33.3 %. CONCLUSIONS: The use of the selective hemosorbent Efferon LPS resulted in significant decreases the hallmarks of systemic inflammation, MOF and requirements for RRT in patients with septic shock.