Introduction: The Paenibacillus genus consists of saprophytic organisms that are commonly associated with soil, water, plants, feces, and diseased insect larvae. Human infection is rare. This disease typically occurs in immunocompromised hosts, adults with a history of intravenous drug use, and hosts with prosthetic medical devices. There are a limited number of case reports describing Paenibacillus infections in neonates. This is the second published instance of pediatric meningoencephalitis caused by Paenibacillus thiaminolyticus in a preterm infant with intrauterine drug exposure. Case Report: A 37-day-old male infant with a history of prematurity of 33 weeks completed gestation presented to the Emergency Department for acute onset poor feeding, poor color, and unresponsiveness at home. Examination revealed cyanosis, apnea, and hypotonia. Vital signs were significant for hypotension and hypothermia. Initial labs revealed a metabolic acidosis, elevated C-reactive protein, normal complete white blood cell count, and a negative viral respiratory pathogen panel. Aerobic blood culture and cerebrospinal fluid (CSF) culture were positive for P. thiaminolyticus within 24 hours. Cranial ultrasound and magnetic resonance imaging revealed changes concerning for liquefactive meningoencephalitis. The infant was admitted to the neonatal intensive care unit (NICU) and ultimately discharged home on a “do not resuscitate/do not intubate” status and later died at 11 months of age. Conclusion: Paenibacillus species are common environmental organisms but can cause devastating disease in neonates. This is the second reported case of a preterm infant with P. thiaminolyticus infection and inutero drug exposure (IUDE), supporting that prematurity and IUDE may be risk factors for severe disease.