Résumé : Background The international prospective COSMOS Registry (NCT05146336) collects real-world data on CytoSorb® (CS) hemoadsorption utilization patterns and outcomes in critically ill patients. This analysis focuses on patients with septic shock. Methods Following informed consent, data was systematically collected before, during, and after CS treatment. Time frame of data collection was from the initiation of COSMOS study enrollment (July 15, 2022) to date of data extraction (May 7, 2025). Study follow-up extended to 90 days. We compared details on vasopressor requirements, fluid balance, and P/F ratio before and after CS treatment. APACHE II was assessed at ICU admission, while SOFA scores were determined at the start and end of CS therapy. Safety of the device was assessed based on investigator-reported device-related adverse effects. Data are presented as either mean ± standard deviation or as median with interquartile ranges (IQR). Results A total of 140 patients (mean age of 61 ± 15 years, 33% female) at 18 study sites treated for septic shock was analyzed. On admission, median APACHE II score was 24 [18,30], SOFA score was 13 [11,15] and Charlson scores of 4 [2,6]. CS therapy was applied as part of kidney replacement therapy (KRT, 85%), standalone hemoperfusion (10%) or extracorporeal membrane oxygenation (ECMO, 5%). On average, each patient received 2.8 ± 2.2 adsorbers, with 47% receiving three or more. CS therapy was associated with a significant reduction in interleukin (IL)-6 levels (from 2,013 [219, 39,988] to 108 [75, 1,662] pg/mL, p < 0.0001) and noradrenaline requirement (0.23 [0.09, 0.43] to 0.07 [0.02, 0.22] µg/kg/min, p < 0.0001), reduced fluid balance (+1,386 [−15, 2,960] to +59 [−738, 1,614] mL, p < 0.0001), and improved oxygenation (P/F ratio 120 [70, 208] to 172 [114, 257], p = 0.0003). CS therapy was also associated with a significantly reduced platelet count (123 [86, 182] to 66 [37, 121] ×109/L, p < 0.0001). Overall SOFA score did not change significantly (p = 0.65), however, system-specific SOFA scores improved significantly for respiratory, cardiovascular and renal sub-scores, while coagulation worsened. Observed ICU mortality was 32.4%. No serious adverse device effects or dysfunctions were reported. Conclusions In this Registry, CytoSorb® therapy was associated with significant early clinical benefits in patients with septic shock, including hemodynamic stabilization and improved fluid balance. Further systematic research is needed to optimize its use and identify patient populations that benefit most.