Measles causes a transient immune suppression, leading to increased susceptibility to opportunistic infections. In experimentally infected non-human primates (NHPs) measles virus (MV) infects and depletes pre-existing memory lymphocytes, causing immune amnesia. A measles outbreak in the Dutch Orthodox Protestant community provided a unique opportunity to study the pathogenesis of measles immune suppression in unvaccinated children. In peripheral blood mononuclear cells (PBMC) of prodromal measles patients, we detected MV-infected memory CD4+ and CD8+ T cells and naive and memory B cells at similar levels as those observed in NHPs. In paired PBMC collected before and after measles we found reduced frequencies of circulating memory B cells and increased frequencies of regulatory T cells and transitional B cells after measles. These data support our immune amnesia hypothesis and offer an explanation for the previously observed long-term effects of measles on host resistance. This study emphasises the importance of maintaining high measles vaccination coverage.