The aim of this cross-sectional study was to determine the prevalence and types of oro-facial lesions and their relationship with the degree of immune suppression in human immunodeficiency virus (HIV)-infected children. This was compared with the prevalence among healthy HIV-negative children. The study was carried out in a tertiary institution in Southwestern Nigeria from May 2005 to March 2006. None of the children in the study had ever been treated with antiretroviral drugs. Thirty-four (87.2%) of 39 HIV infected children and two (9.5%) of the 21 HIV-uninfected children had oro-facial lesions (Fisher's exact, P = 0.0001). In the HIV-infected children, lymphadenopathy was the commonest lesion (82.1%) followed by oral candidiasis (43.6%), gingivitis (25.6%) and bilateral parotid enlargement (25.6%). The most common form of candidiasis was pseudomembranous. All the oro-facial lesions were more common in children with severe immune suppression and were not related to the age, gender or socioeconomic class of the children. It is therefore concluded that there is a high prevalence of oro-facial lesions in HIV-infected children in this study particularly in those with severe immune suppression. These lesions could serve as surrogate markers of HIV infection and aid in initiating prompt diagnosis where routine laboratory investigation for all children at risk is economically not feasible.