Background: C-reactive protein (CRP) is an acute-phase protein reactant that rises especially in response to infectious processes in adults and neonates. It has been used for decades as a tremendous indicator of sepsis in Neonatal in-depth Care devices (NICUs). Aim: This work aims to determine the accuracy of C - reactive protein (CRP), in early diagnosis of late-onset sepsis in infants. Materials and Methods: A systematic search was performed over different medical databases to identify Pediatrics studies, which studied the outcome of CRP in early diagnosis of late-onset sepsis (LOS) in infants. Using the meta-analysis process, either with fixed or random-effects models, we conducted a meta-analysis on sensitivity as a primary outcome, and on specificity as a secondary outcome. Results: Six studies were identified involving 1203 infants. The meta-analysis process revealed that the pooled sensitivity of CRP for diagnosis of late-onset infection=71.7% (p<0.001), and the pooled specificity of CRP for diagnosis of late-onset infection=76.1% (p<0.001). Conclusion: To conclude, late-onset sepsis represents significant morbidity and mortality in the neonatal intensive care unit, CRP plays an important role in the diagnosis of LOS.