Acute parvovirus B19 infection has been implicated in the pathogenesis of several autoimmune conditions, including systemic lupus erythematosus. Viruses, including human parvovirus B19, may trigger bouts of systemic lupus erythematosus in genetically susceptible individuals. Herein, we report on two patients who developed systemic lupus erythematosus associated with acute parvovirus B19 infection and discuss the possible pathogenetic mechanisms implicated.