To assess the incidence and severity of acute kidney injury (AKI) and evaluate risk factors that predict AKI in asphyxiated infants receiving therapeutic hypothermia. Infants ≥36 weeks' gestation diagnosed with moderate-to-severe perinatal asphyxia and received therapeutic hypothermia were reviewed retrospectively (n = 166). Modified Acute Kidney Injury Network criteria were used to diagnose AKI. The results of infants with AKI were compared with the infants who did not develop AKI. AKI developed in 49 (29.5%) infants, of whom 22 had stage I, 13 had stage II, and 14 had stage III AKI. The overall mortality rate was 15.7% and was significantly higher in infants with AKI when compared with infants without AKI (41 vs. 5%; p < 0.001). Asystole at birth (p = 0.044), placental abruption (p = 0.041), outborn status (p = 0.041), need for vasopressor support (p = 0.031), increased bleeding tendency (p = 0.031), initial lactate level (p = 0.015), and 12-hour lactate level (p = 0.029) were independent risk factors for the development of AKI. Receiver operating characteristic curve analysis demonstrated a good predictive value for initial lactate level (>15 mmol/L), with 69% sensitivity (95% CI: 55-82) and 82% specificity (95% CI: 74-89), and for 12-hour lactate level (>6 mmol/L), with 83.7% sensitivity (95% CI: 70-93) and 73.5% specificity (95% CI: 64.5-81), to predict AKI. AKI is still a common complication of perinatal asphyxia despite treatment with therapeutic hypothermia. Identification of risk factors associated with the development of AKI in asphyxiated infants would be potentially beneficial to reduce morbidity and mortality. Besides perinatal risk factors, initial and 12-hour lactate concentrations can be used for the early prediction of AKI.