Pylephlebitis is the septic thrombosis of the portal vein. Hypercoagulability and intra-abdominal sepsis are the main predisposing factors. A 25-year-old man presented to a primary health care center complaining of fever, epigastric pain, and jaundice. He was initially diagnosed with a gastrointestinal infection and alcoholic hepatitis and, due to his unstable clinical status, was referred to the emergency room. A diagnosis of acute pylephlebitis complicated with septic shock was made. Treatment with a wide-spectrum antibiotic and anticoagulation was initiated. Fifteen days later, recanalization of the portal vein was achieved and clinical status was improved. Pylephlebitis following gastrointestinal infection is a potential cause of septic shock.