Latar belakang. Sepsis neonatorum menyebabkan respons inflamasi berlebih sehingga terjadi kerusakan sawar darah otak, disfungsi serebrovaskular dan oksigenasi, gangguan neurotransmiter, degenerasi sel neuron, edema serebral yang berakhir pada kematian sel. Penelitian sebelumnya mendapatkan peningkatan kadar NSE serum pada pasien anak dengan sepsis berat dan syok septik. Tujuan. Mengetahui hubungan kadar NSE serum dengan mortalitas pada sepsis neonatorum. Metode. Digunakan metode analitik observasional kohort prospektif dari bulan Agustus 2015 sampai November 2015. Sampel diambil secara konsekutif dan didapatkan 42 bayi dengan sepsis neonatorum. Analisis statistik diuji dengan regresi logistik dan korelasi Pearson. Orang tua atau wali diminta menandatangani informed consent. Penelitian ini dilaksanakan dibawah persetujuan komite etik. Hasil. Terdapat hubungan antara kadar NSE serum dengan mortalitas (koefisien korelasi r pb =0,738 dengan nilai p<0,001). Cutt-off point kadar NSE serum yaitu 21,9 µg/L dengan sensitivitas 91,3% dan spesifisitas 94,7% dalam menentukan mortalitas pada sepsis neonatorum. Kesimpulan. Semakin tinggi kadar NSE serum maka semakin besar peluang bayi dengan sepsis akan meninggal. Sari Pediatri 2016; 17(6):450-4. Kata kunci: neuron-specific enolase, mortalitas, sepsis neonatorumBackground. Neonatal sepsis causes excessive inflammatory responses, which in turn causes damage to the blood brain barrier, cerebrovascular dysfunction and oxygenation, neurotransmitter disorders, neuron degeneration, and cerebral edema, that ended in the cell death. Previous studies showed elevated levels of serum NSE in pediatric patients with severe sepsis and septic shock. Objective. To determine the relationship of serum NSE levels with mortality in neonatal sepsis. Method. We conducted an observational analytical study with prospective cohort approach from August 2015 until November 2015. Samples were taken consecutively. Forty-two infants with neonatal sepsis were enrolled into the study. The relationship between serum NSE levels with mortality was tested with logistic regression analysis and Pearson correlation test. Informed consent was obtained from parents or guardians. This study was approved by ethical comittee. Results. There is a significant correlation between serum NSE levels with mortality in neonatal sepsis (correlation coefficient r pb = 0.738 with p <0.001). Cut-off point of serum NSE levels to determine risk of mortality is 21.9 µg/L with a sensitivity of 91.3% and specificity of 94.7%. Conclusion. This study shows that the higher levels of serum NSE, the greater chances of newborns with sepsis will die. Sari Pediatri 2016; 17(6):450-4.