HIV infection affects B cell function and is associated with increased immunoglobulin levels, including in HIV-infected pregnant women. It is unknown if maternal HIV infection affects immunoglobulins in their uninfected children. We investigated this using prospective longitudinal data from children born to HIV-infected women enrolled in the European Collaborative Study (ECS). Data from children enrolled in the European Paediatric Hepatitis C Virus Network (EPHN) were used as a comparison group. Associations between infant and maternal factors and child log(10) total IgG, IgM, and IgA levels were quantified in linear regression analyses. A total of 1751 HIV-uninfected (ECS) and 167 HCV-uninfected children (EPHN) were included. HIV-uninfected children had significantly higher IgG, IgM, and IgA levels than HCV-uninfected children up to at least 24 months. Among HIV-exposed uninfected children, IgG levels from birth until 5 years of age were correlated with increased maternal IgG levels. ART exposure in fetal and early neonatal life was associated with lower IgG. These findings indicate alterations in immunoglobulin levels in uninfected children born to HIV-infected women, suggesting that fetal exposure to a chronically activated maternal immune system is associated with an altered humoral response.