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Sepsis is a common and deadly condition affecting the neonatal population. I aimed to understand the causes and outcomes of neonatal sepsis at Children's Hospital 1 in Ho Chi Minh City, Vietnam. A retrospective study from 2013 to 2016 found that Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas spp., coagulase-negative staphylococci (CoNS), Staphylococcus aureus, and Streptococcus pneumoniae were the most common organisms. These organisms were resistant to a wide variety of antimicrobials, which may impact on the efficacy of antimicrobial therapy. I next conducted a prospective study of sepsis in 524 neonates with 69 deaths from January 2017 to June 2018. This group had a mortality of 13.2%; sclerema, leukopenia <4,000/mm3, thrombocytopenia <100,000/mm3, base excess < -20 mEq/L, lactate >4 mmol/L, and hyperglycaemia >180 mg/dL, were associated with death. The major organisms (from 405 isolates) included Klebsiella spp. (6.9%), Escherichia coli (6.7%), Acinetobacter spp. (4.0%), Enterobacter spp. (3.5%), CoNS (57.3%), Staphylococcus aureus (4.4%), and Streptococcus spp. (2.5%). These organisms were highly resistant to all non-carbapenem antimicrobials. The genomics of 15 Acinetobacter baumannii identified sequence type ST570 within genomic complex 2 in 80% of isolates and found the blaOXA-23, blaMBL, blaADC, blaA2, mphE, msrE, and armA AMR genes. A common transposon, carrying blaOXA-23 was associated with widespread carbapenem resistance. In this location, neonatal sepsis was associated with high mortality, complicated clinical features and caused by caused by differing MDR bacteria.