Background <p>Disseminated neonatal enteroviral infection is a rare and life-threatening condition with significant multi-organ involvement. It often presents with nonspecific symptoms that may be mistakenly attributed to bacterial infections. Prompt recognition and treatment are crucial to prevent rapid disease progression. We report two cases of disseminated neonatal enterovirus, including a novel instance of persistent pulmonary hypertension (PPHN) and neonatal stroke.</p> Case presentation <p>A baby boy was delivered vaginally at 35 + 4 weeks, complicated by meconium-stained liquor. He developed respiratory distress after birth, requiring intubation. Subsequently, he developed PPHN, pneumothorax, hypotension, hepatic dysfunction, coagulopathy, and a haemorrhagic stroke, culminating in a decision to re-direct care. He died on day 6 of life. He tested positive for enterovirus from his salivary swab and serum PCR.</p> <p>A baby boy born at 37+2 weeks was delivered in good condition by elective Caesarean section. He was incidentally found to exhibit respiratory distress on day 5 of life, with the rapid development of coagulopathy, hypotension and seizures shortly afterwards. He tested positive for enterovirus on both salivary swabs and serum PCR samples. He achieved a complete clinical recovery and was subsequently discharged home. He continues to remain well at follow-up.</p> Conclusions <p>Hypoxia, coagulopathy and hepatic or metabolic derangement that are inconsistent with the clinical history should raise suspicion of enteroviral infection. Haemorrhagic stroke and PPHN should also be considered as additional manifestations of disseminated enteroviral infection. Prompt recognition can facilitate the administration of intravenous immunoglobulin or antiviral therapy, which may improve survival.</p>