Superior mesenteric vein (SMV) thrombosis is a rare, potentially life-threatening complication of intra-abdominal infection. Here we present a case of massive SMV thrombosis secondary to appendicitis in a 13-year-old boy. He presented with vague abdominal pain and associated symptoms, persistently elevated serum inflammatory markers and a pyrexia of unknown origin. Sonography proved inconclusive, and a definitive diagnosis was made by abdominal contrast-enhanced computed tomography. He was treated with antibiotics and anticoagulation before interval elective laparoscopic appendectomy. The non-specific nature of the presenting symptoms makes SMV thrombosis an important differential to consider when dealing with such patients.