The International Classification of Functioning, Disability and Health (ICF) short-version checklist was used to assess the impairments, activity limitations and participation restrictions experienced by a sample of HIV-positive in-patients admitted to Chris Hani Baragwanath Hospital in Johannesburg, South Africa. Laboratory tests, observation and review of patients' medical records were used to complete the ICF Checklist. Eighty patients were assessed (23 males and 57 females). Common impairments related to the following functions: digestive, metabolic and endocrine systems (83.9%); sensory (83.5%); haematological, immunological and respiratory systems (82.5%); neuromusculoskeletal movement (73.8%); mental (72.6%); energy and drive (75%); sleep (71%); emotional (62%); and muscle power (75%). Activity limitations were present in the area of mobility (56.4%), major life areas (55.1%), and community, social and civic life (50%). Associations found among impairments, activity limitations and participation restrictions were that patients with sensory problems were five-times more likely to have problems in self-care than people without sensory problems. Patients with impairments in the digestive, genitourinary and neuromusculoskeletal systems experienced problems with general tasks (confidence interval [CI]: 4.05–103.03; p < 0.01). Patients with cardiovascular, haematological, immunological and respiratory system problems were 14-times more likely to have problems with execution of general tasks (odds ratio [OR] 14.06, CI: 2.75–71.94; p = 0.002). Activities of participation restriction, difficulties with general tasks and demands (OR 9.68, CI: 1.20–77.92), interpersonal relationships (OR 3.62, CI: 1.09–12.00), domestic life (OR 3.97, CI: 1.12–14.16), and community, social and civic life (OR 4.13, CI: 1.05–16.20) were closely associated with barriers in obtaining products for personal use and using technology. Understanding the prevalence and associations of disability and function in the course of HIV disease may serve as a baseline for developing appropriate and context-sensitive rehabilitation interventions and management strategies for people living with HIV or AIDS.