Background: Cystatin C (CysC) is a renal function marker that is not as influenced as creatinine (Cr) by endogenous or exogenous agents, so it is proposed as a marker in preterm infants. Objectives: To determine serum CysC values in preterm infants during the first week of life, compared to Cr. To analyse alterations caused by prematurity diseases. Method: The design involved a longitudinal, observational study of prospective cohorts. Groups were based on gestational age (GA): Group A (24–27 weeks), Group B (28–33 weeks), Group C (34–36 weeks). Blood samples were collected at birth, within 48–72 h and after 7 days of life. Statistics: SPSS v.20 software was used. The statistical methods applied included chi-squared test and ANOVA. Results: A total of 109 preterm infants were included in the study. CysC levels were 1.54 mg/l (±0.28) at birth, 1.38 mg/l (±0.36) within 48–72 h of life, and 1.50 mg/l (± 0.31) after 7 days (p < 0.05). Cr levels were 0.64 mg/dl (±0.17) at birth, 0.64 mg/dl (± 0.28) within 48–72 h, and 0.56 mg/dl (± 0.19) after 7 days (P < .05). CysC values were lower in hypotensive patients and in those with a respiratory disease (P < .05), and no alterations associated with other diseases were observed. There were no differences in Cr levels associated with any disease. Creatinine levels were higher in patients ≤1.500 g (P < .05). Conclusions: Serum CysC decreased within 48–72 h of life, and this decline showed significance (P < .05). The levels increased after 7 days in all 3 GA groups, and there was no difference in CysC levels among the groups. More studies in preterm infants with hypotension and respiratory disease are required. CysC is a better glomerular filtration rate (GFR) marker in ≤1.500 g preterm infants.