Erythema infectiosum (fifth disease) is the major clinical manifestation of human parvovirus B19 (HPV B19) infection. HPV B19 is known to be associated with adverse effects on fetuses such as hydrops fetalis, aplastic anemia, intrauterine fetal death, and chronic anemia in immunocompromised individuals. The objective of this study was to assess seroprevalence to HPV B19 in three different groups in Shiraz, Iran. The first group included 91 to-be-married girls. The second group included 184 pregnant women and the third group consisted of 184 neonates, who were born to the women in the second group. Specific IgG and IgM antibodies to HPV B19 were measured using ELISA technique. Results showed that the prevalence for IgG to HPV B19 was 56 (61.5%), 127 (69%), and 127 (69%) for the first, second, and third groups, respectively. Overall, 183 out of the 275 (66.5%) women of childbearing age had IgG to HPV B19. The seroprevalence for IgM to HPV B19 was 2.2% for the second group. There was no detectable IgM in umbilical cord sera or in the first group blood samples. In conclusion, approximately one-third of individuals in the study who were of childbearing age were at risk for primary HPV B19 infection.