Fever of unknown origin (FUO) is a common presentation for patients with advanced human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). We prospectively followed 72 patients, consecutively admitted to a Thai regional hospital with FUO and HIV infection to identify aetiologies and mortality in the era of available antiretroviral therapy (ART). Aetiologies of FUO were identified in 67 patients (93%), of whom 61(85%) had an infectious aetiology. The most common infectious aetiologies were Mycobacterium tuberculosis (n=30; 42%), Cryptococcus neoformans (n=17; 24%), Pneumocystis jiroveci (n=9; 13%), Toxoplasma gondii (n=5; 7%), and salmonella bacteraemia (n=5; 7%). Nineteen patients (26%) had co-infection with two or more pathogens. The median CD4 count was 120 cells/mm(3) (range, 1-581 cells/mm(3)), and the all-cause mortality was 22% (n=16). By multivariate analysis, inadequate antimicrobial treatment was the sole predictor of mortality (aOR=4.9; 95% CI=1.2-21.9; P=0.02). Overall, 58 of 72 patients (81%) had an opportunistic infection suggesting that guideline use of ART and prophylactic strategies remain unmet needs that will benefit individuals and populations with HIV/AIDS in Thailand.