A case of duodenal perforation associated with aspirin ingestion in a 21-year old male Nigerian with sickle cell anaemia is reported. He presented with a sudden onset of epigastric pain which later spread to involve other parts of the abdomen. He had previously used aspirin at a dose of 1800 mg daily for two weeks to treat bone pain. Abdominal ultrasonography and X-ray showed fluid collection in the pelvis and elevation of the diaphragm. At exploratory laparotomy, the perforation found in the first part of the duodenum anteriorly was repaired. He was discharged 11 days post-surgery. In view of the frequent usage of salicylates and non-steroidal anti-inflammatory drugs to treat painful crises in sickle cell disease, we suggest careful monitoring of patients on such drugs and those with dyspeptic symptoms must be fully investigated including the use of endoscopy, to prevent fatal outcome.