© 2016, IPNA. Background: Patients with sickle cell disease are at risk for developing chronic kidney disease (CKD). Acute kidney injury (AKI) has been linked to progression to CKD, but limited data exist to determine its role in acute complications of sickle cell disease. We hypothesized that AKI occurs in pediatric patients admitted for acute chest syndrome (ACS) and prolongs hospitalization. Methods: We conducted a 6-year retrospective review of pediatric patients with ACS admitted to a single medical institution. Results: Of the 149 pediatric patients admitted for ACS during the 6-year study period, 12 (8 %) developed AKI. Comparison of patients with and without AKI revealed a significant association between AKI and a larger drop in hemoglobin value from baseline (2.7 vs. 1.4 g/dL; p = 0.003), a lower hemoglobin value at admission (6.4 vs. 7.5 g/dL; p = 0.03), and an increased white blood cell count at admission (33.1 vs. 19.8 × 109/L; p < 0.0001), respectively. AKI (p < 0.0001) together with need for advanced respiratory support (biphasic positive airway pressure or mechanical ventilation) (p < 0.0001) and need for exchange transfusion (p < 0.0001) were associated with prolonged hospitalization. Conclusions: Clinicians should monitor pediatric patients hospitalized for ACS for the development of AKI as a potentially modifiable risk factor for prolonged hospitalization.