Background: One major challenge to the conduct of rigorous neonatal palliative care research is the lack of robust universally agreed upon definitions of key concepts central to pediatric and neonatal palliative care. Objective: We sought to define neonatal serious illness as a foundational concept for neonatal palliative care. Design: Survey study. Setting/Subjects: Practitioners in the United States with expertise in neonatal serious illness. Measurements: Participants ranked 15 components according to how important each would be to include in a conceptual definition of neonatal serious illness. Based on rankings and free text responses, a working definition was created and a follow-up survey was circulated. Participants then ranked the extent to which the proposed definition comprehensively defines neonatal serious illness. The definition was further refined based on responses to the second survey. Results: Eighty experts responded to our first survey. Definition components ranked as most important included "high risk of short term mortality" and "results in shortened lifespan." Analysis of free text responses revealed additional components viewed as important. We developed the following conceptual definition: "Neonatal serious illness 1) carries a high risk of short term mortality OR lifelong medical complexity with probable shortened lifespan, 2) may involve substantial prognostic uncertainty (especially in regard to neurodevelopment) that complicates medical decision-making, and 3) significantly impacts the patient and family's life now or in the future with strain related to treatments and care." Conclusion: We believe our definition of neonatal serious illness will facilitate future study essential to the advancement of care for this population.