We report the case of a patient with rheumatoid arthritis who developed Listeria monocytogenes septic arthritis affecting her total knee arthroplasty during treatment with etanercept. The patient was a 66-year-old female who had suffered from rheumatoid arthritis for 18 years and was treated with etanercept, methotrexate, and prednisolone. After five days from the last etanercept injection, there was acute painful swelling of her left knee joint. In view of hypotension and high fever she was treated for suspected septic shock with intravenous ampicillin 8 grams total daily dose and fluid resuscitation. About 100 ml of moderately cloudy inflammatory synovial fluid was aspirated and Listeria monocytogenes sensitive to ampicillin was grown on culture. After recovery, all prostheses of the left knee were removed, and cement spacers containing vancomycin were inserted. Several hydroxyapatite blocks containing vancomycin were embedded in the cement spacers to maintain sustained-release of the antibiotic. After 3 months from the implant removal, a revision of total knee arthroplasty was performed. During the operation, no infection was identified by means of intraoperative real-time polymerase chain reaction (PCR) and subsequent histopathology findings. The patient recovered and regained mobility on her left knee joint. No infectious symptoms were observed at 1 year after revision of the total knee arthroplasty.