Sepsis, which includes infection followed by inflammation, is one of the leading causes of death among neonates worldwide. The major attribute of this disease process is dysregulated host response to infection leading to organ dysfunction and potentially death. A comprehensive understanding of the host response as well as the pathogen itself are important factors contributing to outcome. Early diagnosis is paramount, as it leads to accurate assessment and improved clinical management. Accordingly, a number of diagnostic platforms have been introduced to assess the presence of blood stream pathogens in septic neonates. Unfortunately, current point-of-care (POC) methods rely on a single parameter/biomarker and thus lack a comprehensive evaluation. The emerging field of biosensing has, however, resulted in the development of a wide range of analytical devices that may be useful at POC. This review discusses currently available methods to screen the inflammatory process in neonatal sepsis. We describe POC sensor-based methods for single platform multi-analyte detection and highlight the latest advances in this evolving technology. Finally, we critically evaluate the applicability of these POC devices clinically for early diagnosis of sepsis in neonates. © 2021 Elsevier B.V.