Introduction: There is a growing number of people with HIV who are aged 50 years or older, and the prevalence of loneliness and social isolation remains unknown. Methods: A multicentre study was conducted across 22 GeSIDA centres. A survey was carried out to assess loneliness [UCLA 3-item Loneliness Scale-3 (UCLA-3)] and social isolation [Lubben Social Network Scale-Revised (LSNS-R)], along with sociodemographic aspects, HIV-related factors, comorbidities, tobacco, alcohol and drug consumption, quality of life, anxiety and depression, and stigma. The prevalence of loneliness (UCLA-3 >= 6) and evident social isolation (LSNS-R = 60 years; 86% were born in Spain; 86.7% in urban areas; 56.4% with secondary or higher education; 4.5% living alone against their wishes. A total of 66.9% were infected through sexual transmission, with a median of 22.9 years since diagnosis [interquartile range (IQR): 12.6-29.5] and a median nadir CD4 count of 245 cells/mu L (IQR: 89-440). Overall, 90.7% had viral load 95%, and 26.3% had a prior AIDS diagnosis. In all, 29.1% and 21% reported significant symptoms of anxiety and depression, respectively, 24.3% had mobility issues, and 40.8% reported pain. Overall, 77.7% of participants reported neither loneliness nor social isolation, 10.0% loneliness only, 5.8% social isolation only and 6.5% both. Multivariable analyses identified that being aged 50-59, unemployed or retired, living alone unwillingly, single, poor quality of life, anxiety, and HIV-related stigma were associated with loneliness. Meanwhile, lower education, living alone unwillingly, and depressive symptoms were associated with social isolation. Individuals living alone unwillingly, with depressive symptoms and experiencing HIV-related stigma were at higher risk for both loneliness and social isolation. Conclusions: There is a relatively high prevalence of loneliness and social isolation in our population. Living alone against one's wishes, being unmarried, and experiencing mobility issues could predispose individuals to feel lonely and socially isolated. Those with anxiety and stigma are more prone to loneliness, while individuals with depression are more predisposed to social isolation. It is necessary to develop strategies for the detection and management of loneliness and social isolation in people with HIV aged >50 years.