Introduction: Sepsis still represents an obstacle in modern medicine. The aim of this study was to evaluate the effectiveness and safety of the combined use of lipopolysaccharide adsorption and haemodialysis (HD) with high cut-off haemofilters as part of the complex intensive care of patients with severe sepsis after cardiac surgery. Methods: The study group included 26 patients, 57 (48-62) years of age, with severe sepsis. The inclusion criteria were clinical signs of severe sepsis (systemic inflammatory response syndrome + infection site + failure of two or more organs) together with endotoxin activity assay (EAA) ≥0.6 and procalcitonin (PCT) levels ≥2 ng/ml. Antimicrobial therapy was initiated in the first hour after the diagnosis of severe sepsis and extracorporeal therapy was initiated within 24 h. All of the patients in the study group received standard therapy. Additionally, they received treatment consisting of two LPS adsorption procedures and HD procedures with high cut-off haemofilters in a single circuit. For the control group, 30 comparable patients, 57 (51-61) years of age, were selected and received only standard therapy. Results: After the last HD procedure within the extracorporeal therapy, we noted an increase in the mean arterial pressure from 76 to 90 mm Hg, p < 0.01, and oxygenation index (from 226 to 291, p < 0.02), in addition to decreases in the LPS concentration according to EAA (from 0.73 to 0.59, p < 0.01) and the Limulus amebocyte lysate test (from 1.44 to 0.36 IU/ml, p < 0.01); PCT falls from 8.19 to 2.44 ng/ml, p < 0.01, and sepsis-related organ failure assessment scores decreases from 13 to 10, p = 0.007. When we compared the data between the study group the day after the procedures and the control group 3 days after the start of intensive care, we discovered that there were statistically significant differences in mean arterial pressure (90 vs. 81 mm Hg, p = 0.0004), oxygenation index (291 vs. 229, p = 0.01), and EAA levels (0.59 vs. 0.67, p = 0.05). Differences in the PCT were not significant (2.44 vs. 3.41, p = 0.15). The 28-day survival rate in the study group was higher than that in the control group (65.4 vs. 33.3%, p = 0.03). Conclusion: The combined use of LPS adsorption and HD with high cut-off haemofilters in conjunction with standard therapy is a safe, effective method for treating patients who have severe sepsis.