Objective  To explore the effects of high cut-off (HCO) membrane continuous venovenous hemodiafiltration  (CVVHDF) on immune function, inflammatory mediator level and organ function in patients with sepsis, and to provide a basis for optimizing the treatment strategy of sepsis.  Methods  Patients with sepsis (including septic shock) requiring continuous renal replacement therapy (CRRT) admitted to the Department of Critical Care Medicine, Baotou Central Hospital from January 2024 to October 2025 were enrolled. They were randomly divided into observation group (HCO group) and control group using the envelope method. T lymphocyte subsets, interleukin-6 (IL-6), procalcitonin (PCT), Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA) score, 28-day mortality, and causes of death were collected before CRRT and 24 hours after treatment.  Results  A total of 80 patients were included. After 24 hours of treatment, the HCO group had higher CD3+%, CD4+%, and CD4+/CD8+ ratios compared with the control group (Z=-2.916, -2.358, -3.873, P=0.004, 0.018, ＜0.001, respectively), and lower CD8+%, IL-6, and SOFA score (Z=-3.387, -1.963, -3.345, P=0.001, 0.049, 0.001, respectively). APACHE Ⅱ score was also lower in the HCO group (t=–4.163, P＜0.001), and the reduction rate of IL‑6 was higher than that in the control group (Z=–2.858, P=0.004). No statistically significant differences were found in PCT level, PCT reduction rate (Z=–1.179, –1.010; P=0.238, 0.312), 28‑day mortality, or causes of death (P=0.522, 0.952) between the two groups.  Conclusion  HCO membrane CVVHDF helps improve organ function in septic patients by effectively removing inflammatory mediators and regulating immune homeostasis.