A prospective study was performed enrolling 11 newborns with neonatal lupus syndrome (NLS) and 22 control newborns to investigate cerebral ultrasound (US) anomalies and their relationship with clinical neurological signs and laboratory findings. Cerebral US detected a significantly higher incidence in the study group of both subependymal pseudocysts (SEPC) and subependymal hemorrhage (SEH), neither of which correlated to autoantibody levels. All infants had completely normal neurological examinations both at birth and follow-up. The etiopathogenesis of central nervous system findings in NLS is discussed. US evaluation identified minimal anomalies compatible with favorable outcome: further studies are necessary to investigate the possible long-term sequelae, pathogenesis and spectrum of cerebral US findings.