While mother-to-child transmission is believed to play in important role in early childhood infection with Kaposi sarcoma-associated herpesvirus (KSHV), the maternal immune response remains largely uncharacterized. This study aimed to characterize the longitudinal humoral response to KSHV in a cohort of HIV-infected Zambian mothers without KS and identify potential factors that may influence transmission. In total, 86/124 (69.4%) mothers were found to be KSHV seropositive. Longitudinal KSHV titers were fairly stable over time, although seroreversion was still common. Of the total 124 mothers, 81 had at least 1 child KSHV seroconvert during the 2 years analyzed, while the remaining 43 mothers had KSHV-seronegative children. Mothers of KSHV-negative children had higher geometric mean titers than mothers of KSHV-positive children; however, there was no difference in the presence of neutralizing antibodies. This suggests that a strong anti-KSHV immune response, and potentially nonneutralizing antibodies, may reduce transmission.