Patients with acquired immunodeficiency syndrome (AIDS) have an increased risk of infectious colitis. While individual cases of infectious colitis are not rare, co-infections involving multiple opportunistic organisms are uncommon. Here, we present an AIDS patient with concurrent opportunistic gastrointestinal infections resulting in symptomatic infectious colitis. A 56-year-old woman with AIDS presented to the hospital with diarrhea, abdominal pain, and sepsis. Initial imagining revealed thickening of the colonic wall suggestive of colitis. The initial workup identified the presence of and through the GI Pathogen Multiplex Polymerase Chain Reaction Panel (bioMérieux BioFire®, Salt Lake City, USA), and stool parasite examination also confirmed the presence of Despite treatment for these infections, the patient's diarrhea persisted. The patient had a sigmoidoscopy performed, and the biopsy results revealed the presence of cytomegalovirus (CMV) Herpes simplex virus (HSV) and The patient subsequently received appropriate treatment for each infection, leading to the resolution of both colitis and bacteremia. This case emphasizes the importance of considering multiple pathogens in the management of infectious colitis in patients with AIDS. The presence of one infectious agent does not preclude the presence of additional agents, and a thorough investigation can ensure a definitive diagnosis and optimal treatment for patients.

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