Recent in vitro studies have investigated the effects of hemoadsorption therapy on endothelial function in sepsis showing a reduction in markers of endothelial dysfunction, but, to this day, there are no clinical studies proving whether this approach could actually positively influence the disturbed vascular barrier function in septic conditions. We retrospectively analyzed data on administered fluid volumes and catecholamines in 124 septic shock patients. We collected catecholamine and volume requirements and calculated the volume balance within different time periods to obtain an assumption on the stability of the vascular barrier. Regarding the entire study cohort, our findings revealed a significant reduction in fluid balance at 72 h (T₇₂) compared to both baseline (T₀) and the 24 h mark (T₂₄). Fluid balances from T₇₂–T₀ were significantly lower in hospital survivors compared with non-survivors. Patients who received a second catecholamine had a significantly lower in-hospital mortality. Our findings suggest that the applied treatment regimen including hemoadsorption therapy is associated with a reduced positive fluid balance paralleled by reductions in vasopressor needs, suggesting a potential positive effect on endothelial integrity. These results, derived from a large cohort of patients, provide valuable insights on the multiple effects of hemoadsorption treatment in septic shock patients.