The progression of HIV disease may be affected by co-infection with other viruses. This study investigates the prevalence of Epstein-Barr virus (EBV); cytomegalovirus (CMV); herpes simplex virus (HSV) types 1 and 2; hepatitis A, B, and C (HA, HB, HC); and tuberculosis in perinatally HIV-infected children. Electrochemiluminescence Immunoassay (EIA) against EBV, CMV, HSV 1 and 2, HAV HBV HCV, and skin testing with purified protein derivative was performed on 45 perinatally HIV-infected children. CMVwas positive in 51%, EBVin 93.3%, HSV-1 in 62.2%, HSV-2 in 48.9%, HAV in 15.6%, HBVand HCV in 6.7% and PPD in 0%. HSV-2 prevalence was higher in females and Hispanics. The prevalence of CMV, EBV HSV-1, and tuberculosis was equivalent to rates reported in the general population. Prevalence of HSV-2 was significantly higher than in the general population (p < 0.001). Higher rates of HSV-2 infection and hepatitis may be secondary to high maternal co-infection rate and subsequent vertical transmission.