Background: Neonatal sepsis is a serious condition with increased morbidity and mortality. Cardiac complications are common sequalae for neonatal sepsis with poor prognosis. Utilization of biomarkers for early detection of these cardiac complications helps in improving the prognosis. Aim of the work: Detect the reliability of plasma copeptin and ischemia-modified albumin (IMA) as indicators of cardiac involvement in neonatal sepsis. Patients and methods: The current study included 70 preterm neonates divided into 3 groups; 30 neonates diagnosed with sepsis and cardiac affection (group 1), 20 neonates diagnosed with sepsis without cardiac affection (group 2) and 20 matched neonates free of sepsis and cardiac affection (group 3). All included neonates had a full history taking, general and local examination. In addition to measuring serum copeptin and IMA levels. Cardiac functions were assessed by transthoracic echocardiography and tissue doppler imaging. Results: A significantly higher mean value of copeptin in group 1 (12.26 ± 4.06 ng/ml), followed by group 2 (4.25±1.56 ng/ml), then group 3 (2.17±0.79 ng/ml) (p<0.001). Also, IMA was significantly higher in group 1 (263.97±81.49 ng/ml), followed by group 2 (68.62±22.08 ng/ml), then group 3 (35.94±10.94 ng/ml) (p<0.001). There was a significant positive correlation between copeptin with IMA. Conclusion: Serum Copeptin and IMA levels are good predictors for detection of cardiac complications in neonatal sepsis besides their role in sepsis detection itself.