Background: Neonatal sepsis is considered one of the major causes of morbidity and mortality in NICUs. To avoid unnecessary treatment of non-infected neonates, emergence of multidrug resistance organisms, prolonged hospitalization and a considerable economic burden, particularly in developing countries with poorly-equipped NICUs, an early, sensitive and specific laboratory test would be helpful to guide clinicians in neonatal units to decide whether or not to start antibiotics. Objective: C-reactive protein (CRP), tumor necrosis factor-a (TNF), interleukin-6 (IL-6) and interleukin-1 (IL-1) were measured in an attempt to identify a set of tests which can confirm or refute the diagnosis of neonatal sepsis at an early stage before administration of antibiotics. Methods: Assessment of serum levels of CRP, TNF-a, IL-6 and IL-1 was done using quantitative enzyme immunoassay sandwich technique in 116 neonates (36 newborns with clinically suspected sepsis, 48 newborns with culture-proven sepsis and 32 infection-free neonates). Results: The cutoff levels for CRP at >12 mg/l had a sensitivity of 91% and specificity of 100%, for TNF-a at >113.2 ng/ml had a sensitivity of 83% and specificity of 100%, for IL-6 at >16.8 pg/ ml had a sensitivity of 100% and specificity of 47%, and for IL-1 at >15 pg/ml had a sensitivity of 100% and specificity of 47% for the diagnosis of infection before antibiotics. * Corresponding