Objective: To observe and explore the effectiveness and safety of continuous blood purification intervention in the clinical treatment of patients with severe sepsis in the Intensive Care Unit (ICU). Methods: Medical records were collected from March 2024 to March 2025, including a total of 54 patients with severe sepsis in the ICU. The patients were divided into two groups using a random number table method: the conventional group (27 patients receiving conventional treatment) and the observation group (27 patients receiving continuous blood purification in addition to conventional treatment). C-reactive protein, arterial lactate, mean arterial pressure, respiration, and heart rate were measured. The Sequential Organ Failure Assessment (SOFA) score was compared, and adverse reactions were observed. Results: The observation group had lower levels of C-reactive protein, arterial lactate, respiration, heart rate, and total SOFA score compared to the conventional group, while the mean arterial pressure was higher (P < 0.05). The incidence of adverse reactions during treatment was lower in the observation group than in the conventional group (P < 0.05). Conclusion: The use of continuous blood purification in the clinical treatment of patients with severe sepsis in the ICU is effective. It can alleviate the disease, improve vital signs, reduce inflammatory damage, and reduce adverse reactions.