Colitis in systemic lupus erythematosus (SLE) poses a diagnostic challenge as clinical, radiological and laboratory findings are often non-specific. Fulminant amoebic colitis is a rare cause of death in SLE. Early diagnosis coupled with timely surgery can reduce the mortality. The demonstration of haematophagous trophozoites in the stool is diagnostic but insensitive. Early endoscopy with adequate specimen collection is an important part of the diagnosis. Serology is both sensitive and specific but can take up to 2-4 weeks for seroconversion making it less useful in a disease that takes a rapid downhill course if treated inappropriately. We report a fatal case of colitis in a patient with SLE due to invasive amoebiasis which was complicated by Salmonella bacteraemia, disseminated intravascular coagulation, acute oliguric renal failure and adult respiratory syndrome. We also reviewed the literature on the clinical features and diagnosis of fulminant amoebic colitis. Amoebic colitis, although rare, should be considered in the differential diagnosis of lupus patients with colitis.