This Guideline provides recommendations on the use of antibiotics for neonates and young infants (0–59 days old) with PSBI in order to reduce young infant mortality rates and is intended for use in resource-limited settings in situations when families do not accept or cannot access referral. It seeks to provide programmatic guidance on the role of community health workers (CHWs) and home visits in identifying signs of serious infections in neonates and young infants. It also provides clinical guidance on the simplest antibiotic regimens that are both safe and effective for outpatient treatment of clinical severe infections and fast breathing (pneumonia) in children 0–59 days old.