This learning activity examines early-onset sepsis in newborns, providing nurses with evidence-based knowledge for recognizing, assessing, and managing this critical condition. The activity covers EOS pathophysiology, risk assessment tools including the Kaiser Permanente Sepsis Calculator, and AAP gestational age-specific management guidelines. Emphasizing nursing assessment skills and family-centered care, the essay prepares nurses to deliver safe, effective care through sophisticated clinical recognition, interprofessional collaboration, and evidence-based interventions.