Background Preterm neonates frequently experience hypernatremia (plasma sodium concentrations >145 mmol/l), which is associated with clinical complications, such as intraventricular hemorrhage. Study design In this single center retrospective observational study, the following 7 risk factors for hypernatremia were analyzed in very low gestational age (VLGA, below 32 weeks) neonates: gestational age (GA), delivery mode (DM; vaginal or caesarian section), sex, birth weight, small for GA, multiple birth, and antenatal corticosteroids. Machine learning (ML) approaches were applied to obtain probabilities for hypernatremia. Results 824 VLGA neonates were included (median GA 29.4 weeks, median birth weight 1170 g, caesarean section 83%). 38% of neonates experienced hypernatremia. Maximal sodium concentration of 144 mmol/l (interquartile range 142–147) was observed 52 hours (41–65) after birth. ML identified vaginal delivery and GA as key risk factors for hypernatremia. The risk of hypernatremia increased with lower GA from 22% for GA ≥ 31–32 weeks to 46% for GA < 31 weeks and 60% for GA < 27 weeks. A linear relationship between maximal sodium concentrations and GA was found, showing decreases of 0.29 mmol/l per increasing week GA in neonates with vaginal delivery and 0.49 mmol/l/week after cesarean section. Sex, multiple birth and antenatal corticosteroids were not associated hypernatremia. Conclusion VLGA neonates with vaginal delivery and low GA have the highest risk for hypernatremia. Early identification of neonates at risk and early intervention may prevent extreme sodium excursions and associated clinical complications.