Abstract Background Cytomegalovirus infection of the gastrointestinal tract is common and is more often seen in patients with acquired immunodeficiency syndrome (AIDS). Although small bowel infection is less common than infection of other parts of the gastrointestinal system, it may lead to perforation, an acute complication, with dreadful results. Case presentation This article reports a case of Cytomegalovirus ileitis with multiple small bowel perforations in a young man with human immunodeficiency virus (HIV) infection. The patient developed abdominal pain with diarrhea and fever, and eventually acute abdomen with pneumoperitoneum. The patient had poor prognosis and deceased despite the prompt surgical intervention and the antiviral therapy he received. At pathology a remarkable finding was the presence of viral inclusions in smooth muscle fibers. The destruction of muscle cells was the main cause of perforation. Conclusion Morbidity and mortality associated with perforation from CMV enteritis in AIDS patients are high and the life expectancy is short. Cytomegalovirus disease is multifocal; therefore, excision of one portion of the gastrointestinal tract may be followed by a complication elsewhere. Our case elucidate that muscle cell destruction by the virus is a significant cause leading to perforation.