This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 µg/kg/h). Hemodynamic parameters (arterial pressure, heart rate, cardiac output, stroke volume variability, left ventricular contractility, systemic vascular resistance, and central venous pressure), vasoactive drug parameters (dose and time of norepinephrine and hourly fluid intake), pulmonary function (partial oxygen pressure and vascular permeability), and cytokines (interleukin-6 and interleukin-10) were observed. Treatment resulted in significant changes at 4-6 h. HVHF was beneficial, as shown by the dose of vasoactive drugs, fluid intake volume, left ventricular contractility index, and partial oxygen pressure. Both CRRT and HVHF groups showed improved removal of inflammatory mediators compared with controls. In conclusion, EFR combined with HVHF improved septic shock in this swine model. The combination decreased shock progression, reduced the need for vasoactive drugs, and alleviated the damage to cardiopulmonary functions.