Despite the lack of literature discussing the topic, the Whipple's Disease (WD) presents higher prevalence in people with compromised immunity, as it happens in HIV. This association can be seen in the current case, which reports a male patient, middle-aged, positive sorologic status for HIV with irregular use of antiretroviral therapy (ART) who presented symptoms of diarrhea and malabsorption during a previous hospitalization for pneumothorax treatment. In a biopsy of the small intestine, by upper gastrointestinal endoscopy, the diagnosis of Tropheryma whipplei infection was possible through immunohistochemical examination for periodic-Shiff acid (PSA), with evidence of foamy macrophages with cytoplasm rich in PSA positive granules. The medical conduct was the empirical treatment for pseudomembranous colitis, which includes association of Meropenem, Vancomycin and Metronidazole. With the improvement of the clinical of malabsorption and the decrease of diarrheal episodes the patient got hospital discharge. Yet underdiagnosed in people living with HIV, the WD should be considered in the arise of compatible symptoms, because when treated on time the prognosis of the disease is usually favorable.