AIM To evaluate the diagnostic value of interleukin-6 (IL-6) to predict the likelihood of neonatal sepsis in order to design an algorithm to decide antibiotic therapy. METHODS IL-6 and C-reactive protein (CRP) were determined in 42 newborns with clinical suspicion of infection. Newborns were classified as a confirmed, probable or no infection, based on the results of cultures, chest X-rays and the involvement of four or more clinical areas on a scale of eight. Samples for IL-6 were collected in the initial assessment and frozen until its determination at the end of the study. Blinded IL-6 measurements were performed using a rapid test. Receiver operator characteristics curves (ROC) for CRP and IL-6 versus infection (confirmed or probable) were determined. RESULTS Among the 42 cases included in the study 11 (26.2%) were classified as confirmed or probable infection. The area under curve (AUC) for IL-6 was 0.9, with a cut-off value of 53 pg/ml: sensitivity 90.91%, specificity 80%, positive predictive value (PPV) 62.5% and negative (NPV) 96% The level of IL-6>96 pg/ml and/or the combination of IL-6>53+CRP>13.3 mg/l, were the markers that best predicted infection: specificity 100% and PPV: 100%. CONCLUSIONS Assessment of IL-6 could allow withholding or early discontinuation of antibiotics in newborns with IL-6<54 pg/ml. In cases with IL-6>96 pg/ml and/or IL-6>53+ CRP>13.3, antibiotics should be started promptly, given the high likelihood of infection. Implementation of an algorithm based on the determination of IL-6 and CRP, in the initial assessment of the newborn with clinical suspicion of infection, could reduce unnecessary antibiotic therapy.