Introduction: Neonatal Acute Kidney Injury (AKI) become a serious problem in critically ill neonates, serum creatinine level (SCr) which used to detect glomerular filtration rate has a lot of pitfalls, serum cystatin C level (SCys C) is more accurate and with better advantages. Aim of the Study: Our aim is to early detection of acute kidney injury in neonates especially low birth weight before any damage occur. Methods: This cross sectional study was conducted on 50 critically ill neonates randomly selected from the Neonatal Intensive Care Unit, Pediatric Department, in our University Hospitals. Detailed history, clinical examination, appropriate investigations were done. Plasma level of serum Cystatin C as well as SCr were done at the 1st and 3rd day of admission. Results: Fifty infants were recruited into this study out of which complete data were available, the study was conducted on both term and preterm infants. The mean SCr level in AK I group in the 1st and 3rd day respectively was 0.56 and1.13, while serum cystatin level was 31.86 and48.67 respectively with significant P Value P ≤ 0.001, SCr had a significant correlation with weight (r = 0 .992; P < 0.001), whereas serum CysC had no correlation with the infant’s weight (r = 0.021; P = 0.884). There was no statistically significant difference in SCr and CysC between male and female infants. Conclusion: Serum Cystatin C is an earlier detector for AKI in critically ill neonates and un like serum creatinine has no significant correlation with birth weight.