Neonatal sepsis remains a very common cause of morbidity and mortality. Point-of-care ultrasound imaging is a useful tool to determine the site of infection, the progress of sepsis, and prognosis/outcomes of septic neonates. The organ system imaging that is useful includes cardiac ultrasound for delineation of the hemodynamics, cranial imaging for changes in meningitis/ventriculitis, lung ultrasound for early detection of effusions and consolidation, and gut imaging for gut perfusion and viability in necrotizing enterocolitis. We describe the role of ultrasound imaging in the early diagnosis and management of neonatal sepsis.