Background <p>In preterm neonates, the postnatal course of serum creatinine (sCr) is influenced by maternal sCr levels and physiological changes. While transient postnatal increases have been reported, the relationship between the initial value at birth (Cr₀) and subsequent changes to the peak value (ΔCr) remains unclear.</p> Methods <p>Among 467 eligible preterm neonates admitted to neonatal intensive care unit, after excluding those with conditions or treatments affecting circulatory dynamics, the postnatal day of peak sCr was determined according to gestational age. Among these, 225 neonates with available Cr₀ and sCr values on the peak day were included in analyses of ΔCr. Simple linear regression was performed to evaluate the correlation between Cr₀ and ΔCr, and multiple regression to identify factors associated with ΔCr.</p> Results <p>The sCr peak occurred on day 2 in neonates with gestational age ≤ 29&#xa0;weeks and on day 1 in neonates with gestational age ≥ 30&#xa0;weeks. Simple regression revealed a significant correlation between Cr₀ and ΔCr (ΔCr = 0.602 − 0.635 × Cr₀, R² = 0.423, <i>P</i> &lt; 0.001); ΔCr was zero when Cr₀ was 0.95&#xa0;mg/dL. Multiple regression identified Cr₀ (β =  − 0.701, <i>P</i> &lt; 0.001), 5-min Apgar score (β =  − 0.014, <i>P</i> = 0.008), and 24-h urine output (β =  − 0.039, <i>P</i> &lt; 0.001) as independent factors.</p> Conclusions <p>Neonatal sCr levels change during the early postnatal period, and the regression analysis identified a balance point at 0.95&#xa0;mg/dL. These findings may aid interpretation of sCr changes when assessing acute kidney injury in preterm neonates.</p> Graphical Abstract <p>A higher resolution version of the Graphical abstract is available as Supplementary information</p> <p></p>