Aims: A previous study reported hemolytic crisis in patients with erythro-enzymopathy. Here, we report two further cases of massive acute hemolysis with methemoglobinemia in two siblings with glucose dehydrogenase deficiency and parvovirus B19 (PAVB) infection. Presentations of Case: The first was his 8-year-old brother, who developed mild hemolysis with liver dysfunction and survived. The second patient was a 10-year-old boy, who developed liver and kidney failure and died. To elucidate the mechanisms through which PAVB can cause liver and kidney failure, we analyzed cytokines and virus burden. Conclusion: Physicians should be aware that severe hemolysis may occur in patients with hematological abnormalities and PAVB infection.