Background: Commonly in newborns, acute kidney injury (AKI) to be linked to poor clinical outcomes, which in turn is linked to higher rates of morbidity and mortality. Caffeine administration may save low-birth-weight newborns from acute renal injury. Objectives: This study aimed to explore the relationship between caffeine citrate administration and AKI in preterm neonates in the first 7 days after delivery, and to test the hypothesis that caffeine administration would be linked with lower frequency and severity of AKI. Methods:  This study included 68 preterm neonates of both sexes from the NICU of Menoufia University who were divided into 2 groups. Group I comprised (34) preterm neonates who received caffeine citrate. Group II comprised (34) preterm neonates who did not receive caffeine citrate. Results: There was no statistically significant difference in urea and creatinine levels among the studied groups in the first while there was a statistical difference in the third and seventh days as those who received caffeine citrate showed lower values than those who did not receive caffeine citrate. There was a statistically significant difference between the two groups in AKI staging as the majority (82.4%) of cases in group I was stage 0 while near to half (58.8%) of cases in group two were stage 1. There was no statistically significant difference between the two groups as regards consanguinity and delivery, while there was statistically significant difference between group I and group II as regards gestational age, weight and Apgar score 1 and 5 (P =0.001). Conclusion: Giving caffeine to premature neonates was linked to a lower incidence of AKI.