Objective To explore the risk factors of chronic kidney disease (CDK) in premature infants and low birth weight infants. Methods Cases of low birth weight and premature infants from three key hospitals in Sanya, Hainan Province were collected in this study from January 2005 to January 2019. All traceable children were followed up for 18 months to observe the screening rate of CKD. The clinical data after birth, the laboratory examination data after enrollment and the results of follow-up data were analyzed. Logistic regression analysis was used to observe the risk factors of CKD in preterm and low birth weight infants. ROC curve analysis was used to observe the effectiveness of each risk factor in evaluating CKD. Results A total of 1 269 subjects were included in the study, of whom 39(3.07%) cases were diagnosed with CKD. Binary Logistic regression analysis showed that gestational age ≥29.37 weeks, endogenous creatinine clearance (Ccr)≤36.53 ml/(min·1.73 m²), serum albumin≥39.43 g/L, and exercise behavior index≥10.17 were the protective factors for preterm infants and low birth weight infants from CKD (β=-0.290,-0.117,-0.038,-0.559,P<0.05), serum creatinine (Scr)≥47.58 μmol/L, diastolic blood pressure≥85.69 mmHg, urine albumin≥12.16 mg/L, fasting blood glucose≥5.61 mmol/L were risk factors for CKD in preterm infants and low birth weight infants (β=0.047,0.069,0.315,1.510,P＜0.05). ROC analysis showed that Ccr, serum albumin, diastolic blood pressure, blood creatinine, urine albumin, fasting blood glucose, and exercise behavior index had certain value in predicting CKD in preterm infants and low birth weight infants (P<0.05), and Ccr and Scr had better predictive performance (AUC =0.794,0.738). Conclusions Scr diastolic blood pressure, urine albumin, and fasting blood glucose are risk factors for CKD in preterm infants and low birth weight infants. High exercise index, high serum albumin, and high gestational age are beneficial to reduce CKD in premature and low birth weight infants. Ccr and Scr can predict the occurrence of CKD in preterm infants and low birth weight infants, but attention should be paid to the identification of false positive cases.