Background: : Neonatal sepsis is the most common cause of neonatal mortality in Lao PDR, however, there are limited contemporary data on the incidence of early-onset sepsis in Lao PDR. Antibiotics are most commonly used in intensive care units and intermediate care unit for maternal risk and clinical signs of early-onset neonatal sepsis. Objectives: : To describe early-onset neonatal sepsis by clinical signs, laboratory results, and antibiotic usage in neonates admitted to Mother and Newborn Hospital and Mahosot Hospital in Vientiane, Lao PDR Methodology: : This study is a descriptive study of neonates admitted within 3 days of life, early-onset neonatal sepsis was defined as a neonate who presented with two or more clinical signs or laboratory results suggesting sepsis and received antibiotics for at least 3 days. Results: : Among 500 cases the common clinical presentations of EOS are oxygen requirement or need for ventilation support in 304 infants (60.8%) temperature instability in 223 infants (44.6%) and increased serum bilirubin in 154 infants (30.8%) There were 13 infants (2.6%) diagnosed with culture-proven sepsis from positive blood culture. The causative organisms were predominantly gram-negative bacilli such as Escherichia coli, and Acinetobacter baumannii, and gram-positive cocci such as Staphylococcus aureus, and Group B Streptococci. The rate of antibiotic usage is very high, ampicillin was prescribed in 489 (97.8%) and gentamicin in 438 infants (87.5%), the duration of antibiotic therapy was 5 to 14 days. Conclusion: The rate of culture-proven early-onset neonatal sepsis was low, but there was a very high rate of antibiotic usage. Antibiotic stewardship should be strongly emphasized.