Now that the majority of people living with HIV take combination antiretroviral therapy (ART), the spectrum of causes of pyrexia of unknown origin (PUO) has changed compared with the pre-ART era. In these guidelines, we focus on causes and evaluation of PUO among people living with HIV with CD4 counts <350 cells/mm3 . Causes of PUO in people living with HIV with higher CD4 counts are likely to be similar to those in HIV-negative individuals. Therefore, for those with higher CD4 counts we recommend following guidance for management of PUO in the general population [1-3], with the caveat that some infections, for example invasive pneumococcal disease [4] and tuberculosis (TB) [5], are more common among people living with HIV than those without HIV even on ART and with higher CD4 counts. Infective, inflammatory, neoplastic and miscellaneous causes need to be considered in all cases. HIV alone is rarely a cause of PUO, and other possible causes should always be investigated.