Acute kidney injury (AKI) is a complex disorder with clinical manifestations ranging from mild dysfunction to complete kidney failure. The published literature on the incidence and outcome of AKI in the critically ill neonatal population is scarce. The aim of this study was to evaluate the types, the associated risk factors and short-term outcome of AKI in the critically ill neonates. A cohort study was conducted including 100 critically ill neonates successively admitted to the Neonatal Intensive Care Unit. The inclusion criteria were a gestational age ≥28 weeks and body weight ≥1 kg. Exclusion criteria included those with multiple congenital anomalies or on drugs altering glomerular filtration rate or AKI developing postoperatively. Neonates were evaluated for the development of AKI [creatinine >1.5 mg/dL and/or blood urea nitrogen (BUN) >20 mg/dL] and were assigned as group A (who developed AKI) and group B (who did not develop AKI). Forty-one patients developed AKI (group A) among whom nine (22%) showed oliguric AKI. The most common risk factors among group A patients were sepsis (75.6%) and nephrotoxic drug administration (75.6%), followed by shock (39%). There were no statistically significant differences between both groups except for male sex predominance and necrotizing enterocolitis (NEC), which were significantly higher among group A (P <0.05). Use of continuous positive airway pressure (CPAP) ventilation was significantly higher in neonates without AKI (13.6% vs 0.0%, P = 0.02). The mortality rate among group A reached 51.2%. Various risk factors including gender, gestational age, birth weight, shock, NEC, sepsis, nephrotoxic drugs, oliguria and mechanical ventilation were studied as regards outcome of group A, and all factors except gender and oliguria proved to be significantly higher in deceased neonates. Male sex and NEC were important risk factors for developing AKI that was predominantly non-oliguric. CPAP ventilation may have a protective effect against AKI. The mortality rate was more than three times higher in the AKI group.