Abstract Human parechovirus-3 (HPeV-3) has been reported to cause a sepsis-like illness in neonates and young infants. We experienced the occurrence of HPeV-3 infection in nine neonates and young infants (eight boys, one girl; aged 14–52 days, median 31 days). They were admitted to our hospital with the chief complaints of fever persisting for 3–5 days (median 4 days) and lethargy. Five infants presented with abdominal distension and six had a rash (including acral reddening), as was previously reported with this viral infection. Abdominal distension with navel protrusion and acral reddening during the course were characteristic. Laboratory data were characterized by elevated values for serum AST, LDH, FDP, D-dimer, ferritin, soluble IL-2 receptor, triglyceride, choline esterase, and urinary β2 -microglobulin. Two of our nine patients presented with a hemophagocytic lymphohistiocytosis (HLH)-like illness and required specific therapy. These data suggest that HPeV-3 is an important virus that can cause hypercytokinemia, which sometimes leads to HLH, and systemic inflammatory response syndrome in neonates and young infants.