Early-onset neonatal sepsis (EOS) remains a significant problem for neonates, particularly preterm infants. Group B Streptococcus (GBS) is the most common cause, while Escherichia coli is the leading cause of mortality. Maternal intrapartum antimicrobial prophylaxis has reduced GBS disease but increased Gram-negative infections, especially in very-low-birth-weight infants. Diagnosis of EOS combines clinical presentation, nonspecific markers like C-reactive protein and procalcitonin, blood cultures, and molecular methods like PCR. Cytokines and cell surface antigens are also being studied as screening tools. Viruses like enteroviruses, parechoviruses, and HSV should be considered in the differential diagnosis. Empirical treatment is based on local antimicrobial resistance patterns, typically using ampicillin and gentamicin or ampicillin and cefotaxime if meningitis is suspected. Current research focuses on developing vaccines against GBS. EOS is defined as infection occurring within 72 hours of birth in preterm infants and within 7 days in term infants. Late-onset sepsis (LOS) occurs after these times. Risk factors include maternal and infant factors, such as maternal fever, prolonged membrane rupture, and preterm birth. GBS is a Gram-positive diplococcus with virulence factors like its polysaccharide capsule. It is asymptomatic in pregnant women but can cause severe infections in newborns. E. coli is the second leading cause of EOS, especially in preterm infants. Listeria monocytogenes is a Gram-positive bacillus that can cause sepsis in preterm infants. Gram-negative rods, including E. coli, Klebsiella, and Enterobacter, are important causes of LOS and are increasingly associated with antimicrobial resistance. Coagulase-negative staphylococci and Staphylococcus aureus are more common in late-onset sepsis. Fungal infections, particularly Candida, are rare in EOS but more common in late-onset sepsis. Herpes simplex virus (HSV) can cause sepsis in neonates, often presenting as disseminated infection. Enteroviruses and parechoviruses are also implicated in EOS and can present with sepsis-like symptoms. Clinical presentation of EOS varies by gestational age and infection severity. Preterm infants often present with apnea, bradycardia, and cyanosis. Term infants may present with respiratory distress, which can mimic other conditions. Laboratory findings include white blood cell counts, platelet counts, and blood cultures. Acute-phase reactants like C-reactive protein (CRP) and procalcitonin (PCT) are used to assist in diagnosis. Molecular testing, including PCR, is increasingly used for rapid detection of pathogens. Biomarkers like IL-6, IL-8, TNFEarly-onset neonatal sepsis (EOS) remains a significant problem for neonates, particularly preterm infants. Group B Streptococcus (GBS) is the most common cause, while Escherichia coli is the leading cause of mortality. Maternal intrapartum antimicrobial prophylaxis has reduced GBS disease but increased Gram-negative infections, especially in very-low-birth-weight infants. Diagnosis of EOS combines clinical presentation, nonspecific markers like C-reactive protein and procalcitonin, blood cultures, and molecular methods like PCR. Cytokines and cell surface antigens are also being studied as screening tools. Viruses like enteroviruses, parechoviruses, and HSV should be considered in the differential diagnosis. Empirical treatment is based on local antimicrobial resistance patterns, typically using ampicillin and gentamicin or ampicillin and cefotaxime if meningitis is suspected. Current research focuses on developing vaccines against GBS. EOS is defined as infection occurring within 72 hours of birth in preterm infants and within 7 days in term infants. Late-onset sepsis (LOS) occurs after these times. Risk factors include maternal and infant factors, such as maternal fever, prolonged membrane rupture, and preterm birth. GBS is a Gram-positive diplococcus with virulence factors like its polysaccharide capsule. It is asymptomatic in pregnant women but can cause severe infections in newborns. E. coli is the second leading cause of EOS, especially in preterm infants. Listeria monocytogenes is a Gram-positive bacillus that can cause sepsis in preterm infants. Gram-negative rods, including E. coli, Klebsiella, and Enterobacter, are important causes of LOS and are increasingly associated with antimicrobial resistance. Coagulase-negative staphylococci and Staphylococcus aureus are more common in late-onset sepsis. Fungal infections, particularly Candida, are rare in EOS but more common in late-onset sepsis. Herpes simplex virus (HSV) can cause sepsis in neonates, often presenting as disseminated infection. Enteroviruses and parechoviruses are also implicated in EOS and can present with sepsis-like symptoms. Clinical presentation of EOS varies by gestational age and infection severity. Preterm infants often present with apnea, bradycardia, and cyanosis. Term infants may present with respiratory distress, which can mimic other conditions. Laboratory findings include white blood cell counts, platelet counts, and blood cultures. Acute-phase reactants like C-reactive protein (CRP) and procalcitonin (PCT) are used to assist in diagnosis. Molecular testing, including PCR, is increasingly used for rapid detection of pathogens. Biomarkers like IL-6, IL-8, TNF