Lemierre's syndrome is characterized by a primary oropharyngeal infection in a young healthy person who subsequently develops septic thrombophlebitis of the internal jugular vein and metastatic abscesses. We here report an uncommonly severe case of Lemierre's syndrome with acute respiratory distress syndrome (ARDS), in which polymyxin B-immobilized fiber (PMX) was used as supportive therapy. A 30-year-old, previously healthy man presented with sore throat, fever, rigor, and dyspnea. Chest computed tomography scan revealed multiple bilateral peripheral pulmonary nodules with small bilateral pleural effusions. The patient's condition rapidly deteriorated into ARDS after admission. Intubation followed by mechanical ventilation was required, and hemoperfusion with PMX was useful in alleviating the patient's condition. Isolation of Fusobacterium necrophorum from the blood culture and the contrast-enhanced scan revealed thrombosis and thrombophlebitis in the left internal jugular vein. The patient was diagnosed with Lemierre's syndrome, and an alternative treatment regimen with prolonged administration of ampicillin, clindamycin, and metronidazole resulted in improvement of the patient's respiratory function and general condition. Our case indicated that PMX might be an effective supportive therapy in severe cases of Lemierre's syndrome with ARDS that possessed no indication of surgical interventions.