Erythema infectiosum, also commonly known as fifth disease, is a common, usually self-limited illness caused by parvovirus B19 infection. In most cases, recovery from parvovirus infection results in lifelong immunity. Unfortunately, the clinical manifestations of parvovirus B19 can be more serious, especially in immunocompromised patients or during pregnancy, in which it can be transmitted to the fetus. Infection can also be commonly present as anemia related to decreased red-blood-cell production; small joint arthropathies are also common, especially in adults. Infrequently, parvovirus B19 infection can present in diverse ways, including encephalitis, nephritis, vasculitis, or myocarditis, among other inflammatory conditions. We present a longitudinal pediatric case of parvovirus B19 infection that highlights a myriad of challenges arising from an initial straightforward case of fifth disease.