['Early onset sepsis (EOS) remains a major cause of mortality and morbidity in neonates, and traditional clinical markers effective for adults are less effective in these patients. This study aimed to assess the value of individual plasma biomarkers as well as biomarker combinations for predicting EOS in neonates.', 'This prospective study included 151 neonates with suspected EOS. Plasma levels of interleukin (IL)-27, IL-6, IL-8, tumor necrosis factor (TNF)-α, heat shock protein (HSP) 70, macrophage inflammatory protein (MIP)-1α, MIP-1β, granzyme B, and matrix metalloproteinase (MMP)-8 were measured through multiplex cytokine profiling and assessed along with C-reactive protein (CRP) and procalcitonin (PCT). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of biomarkers individually and in combination. Logistic regression model was constructed to identify independent predictors of EOS.', 'The proven sepsis and probable sepsis groups were combined to form the infected group (n\u200a=\u200a68), and the possible sepsis and low-risk sepsis groups were combined to form the uninfected group (n\u200a=\u200a83). The ROC area under the curve was 0.747 for IL-27(p\u200a<\u200a0.01). In addition, IL-6, TNF-α, HSP 70, MMP-8, PCT, and CRP were significantly predictive of EOS, whereas IL-8, granzyme B, MIP-1α, and MIP-1β were not. Both IL-27 and PCT were identified as independent predictors of EOS in the multivariate model, and the combined use of these markers showed significantly increased predictive ability for EOS.'] Does multiplex Cytokine Profiling identify Interleukin-27 as a Novel Biomarker for Neonatal Early Onset Sepsis?