This study evaluates the impact of hemoperfusion (HP) on 28-day mortality in leptospirosis patients with renal failure and septic shock. A total of 37 patients were randomized to receive either standard medical therapy (SMT) or SMT with HP. The HP group showed a 36.84% risk reduction in 28-day mortality and significant improvements in inflammatory markers, renal function, and pulmonary function. Hemoperfusion was shown to be a safe and effective adjunct therapy, promoting faster recovery and increased survival rates.