Background <p>Hemoadsorption is increasingly used as adjunctive extracorporeal support in sepsis and septic shock. Comparative data on device-specific hematologic effects remain limited. CytoSorb^® and oXiris^® are among the most widely applied hemoadsorption devices, but their impact on blood element kinetics has not been fully characterized.</p> Methods <p>In a prospective single-center observational study, 66 patients with sepsis or septic shock underwent hemoadsorption combined with continuous renal replacement therapy (CRRT) using either CytoSorb^® (<i>n</i> = 36) or oXiris^® (<i>n</i> = 30). Hemoglobin (Hb), hematocrit (Hct), erythrocytes (RBC), and platelets (PLT) were measured prior to and following hemoadsorption. Descriptive analyses and statistical tests were employed to evaluate between-group differences in hematologic parameters. Clinically relevant declines defined as ≥ 15% reduction in Hb, Hct, and RBC, and ≥ 50% in PLT were treated as events in time-to-event (TTE) analysis.</p> Results <p>CytoSorb^® was associated with significant reductions in Hb, Hct, RBC, and PLT, while no statistically significant hematologic changes were observed with oXiris^®. TTE analyses showed that CytoSorb^® led to faster declines across all parameters in reaching predefined reductions. Median times to predefined thresholds ranged from 19.6 to 27.6&#xa0;h with CytoSorb^®, compared with 38.9 to 42.1&#xa0;h with oXiris^®, despite shorter treatment duration in the CytoSorb^® group.</p> Conclusion <p>CytoSorb^® hemoadsorption results in more pronounced and faster hematologic deterioration compared with oXiris^®, indicating meaningful device-specific differences in blood element kinetics during extracorporeal therapy. Close hematologic monitoring is particularly important when CytoSorb^® is used. Larger multicenter studies with mechanistic biomarkers are needed to validate these findings.</p>