Recipients of allogeneic hematopoietic stem cell transplant can develop life-threatening complications at any time following their transplants. These complications require repeated clinical assessment, appropriate and thorough screening as well as a comprehensive management approach. We report a young adult male who received a sibling allograft in the second complete remission of his acute lymphoblastic leukemia at King Faisal Specialist Hospital and Research Centre in Riyadh. The patient developed severe colitis which was caused by: acute exacerbation of chronic graft versus host disease of the lower gastrointestinal tract, cytomegalovirus disease of the colon and a superadded Salmonella infection caused by food poisoning. The multifactorial colitis was properly investigated and successfully managed. To our knowledge, this is the first case of multifactorial colitis in a recipient of hematopoietic stem cell transplant.