Background. Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory and demyelinating disorder of the central nervous system, with a distinct tendency to a perivenous localization of pathological changes. Children are the most affected population and frequently presented after exanthematous viral infections or vaccination. Due to the rarity of this disease, the annual incidence rate in the population is not precisely known. Case Presentation. Here, we present a 28-year-old male HIV-1 positive patient with an acute confusional state, a diminished alert status characterized by somnolence, hypoprosexia, and complex visual hallucinations. Neuroimages reported white matter demyelinating lesions, mainly affecting the semioval centers, the frontal lobe, and the left parietal lobe; hypointense on T1-weighted images, hyperintense on T2-weighted images and fluid-attenuated inversion recovery weighted images, DWI with restricted diffusion, and a parietal ring-enhancing lesion after IV gadolinium administration. Discussion. In HIV positive patients, the demyelinating disorders have a broader clinical spectrum that could be explained by the immunosuppressed state of the patients, the evolution of the disease, the use of medications, the opportunistic infections, and the environment. Due to this highly variable clinical spectrum, ADEM is a significant challenge for the physicians in HIV positive patients, causing a delay in the diagnosis and treatment. Conclusion. We suggest that ADEM should be considered among the differential diagnosis in HIV-infected patients with focal or multifocal neurological symptoms, particularly in encephalopathies with multifocal central nervous system involvement without severe immunosuppression.