Objective: To evaluate the clinical significance of serum albumin (ALB) levels in the early evaluation and prognosis of preterm infants in the neonatal intensive care units (NICUs). Materials and Methods: The authors collected and retrospectively analyzed complete clinical records of preterm infants admitted to the NICU from July 2012 to March 2013. The cases were divided into three groups according to their ALB levels: ≥30 g/L, 25–30 g/L, and ≤25 g/L. Results The mean gestational age in the ≤25 g/L ALB group was significantly higher than that in the ≥30 g/L ALB group [(33.41 ± 2.15) weeks] (p < 0.05). The prealbumin, blood platelet, and blood urea nitrogen in the ≤ 25 g/L ALB group were significantly lower than those in the > 30 g/L ALB group (p < 0.05). In addition, serum lactate in the ≤ 25 g/L ALB group was significantly higher than that in the ≥ 30 g/L ALB group (p < 0.05). Conclusion Serum ALB level increased with increasing gestational age. Lower ALB levels were associated with more perinatal complications, damage to multiple organs, more severe cases, and mechanical ventilation, which resulted in longer hospital stays and poorer prognoses.