Enterovirus and human parechovirus (HPeV) are RNA viruses belonging to the family Picornaviridae that frequently infect infants. These infections show a wide variety of clinical manifestations, from mild to severe. However, there are no known early clinical markers for diagnosis and prediction of disease severity. The aim of this study was to examine the clinical utility of urinary beta 2-microglobulin (β2MG) for the early detection and prognosis of infantile enterovirus and HPeV infections.This retrospective study included 108 full-term infants younger than 60 days of age, including 15 with enterovirus or HPeV-3 (enterovirus/HPeV-3), 22 with respiratory syncytial virus (RSV), and 24 with bacterial infections. Laboratory data and clinical characteristics were compared among these 3 groups. Of the 15 patients with enterovirus/HPeV-3, 6 were treated with intravenous immunoglobulin (IVIG subgroup) because of severe clinical conditions.Urinary β2MG to creatinine ratio (β2MG/Cr) was significantly higher in the enterovirus/HPeV-3 group compared to bacterial and RSV infection groups (both P < .001). In the enterovirus/HPeV-3 group, mean peak urinary β2MG/Cr was observed on day 1 or 2. Urinary β2MG/Cr values were significantly higher in the IVIG subgroup than the non-IVIG subgroup (P < .001).Increased urinary β2MG/Cr in early-stage infection may be a useful clinical marker for the detection and prediction of infantile enterovirus and HPeV infection severity.