Post-polypectomy syndrome (PPS) results from electrocoagulation injury to the bowel wall that induces a transmural burn and localized peritonitis. It has a good prognosis; however, there are exceptions when complications are observed. We here report a case of a 50-year-old man who developed lumbosacral pain and high fever with chills four days after colonoscopy, during which polypectomy was performed by endoscopic mucosal resection (EMR) and argon plasma coagulation (APC). Both the plain abdominal film and abdominal CT scan showed no free air, and lumbar CT showed no apparent lesions, which satisfied the diagnosis of PPS. However, the patient was in a critical condition as he developed septic shock caused by bacteremia. Following active treatment, the patient's condition rapidly improved. Therefore, we suggest that clinicians should consider the severity of PPS with sepsis and colon transmural burn. Patients with a diagnosis of PPS should be admitted to the hospital for observation and treatment to avoid adverse consequences.