Background: Recent guidelines for preterm parenteral nutrition (PN) recommend an earlier and higher intake of amino acids (AA) and energy to avoid postnatal catabolism and approximate normal foetal growth. Few investigations explored how early PN may affect electrolyte and water homeostasis. We performed a prospective observational trial to assess the effect of nutrient intake on electrolyte homeostasis and balance. Methods: During 16 months all infants ≤32 weeks were eligible. In the first week of life we recorded daily: electrolytes (plasma and 8-hour urine collection), nutritional intake, urine output, body weight and we calculated sodium (Na) and potassium (K) balance. Infants were divided, for analysis, into 3 groups of AA intake: Low <1.5g/kg/day (LAA); Medium 1.5-2g/kg/day (MAA) and High >2g/kg/day (HAA). Results: 154 infants were included. HAA group presented lower weight loss. Na balance was influenced by urine output and postnatal age, with little contribution of nutrition. Kalemia and K balance were mainly influenced by AA intake. K balance differed among groups: LAA -2.3 mol/kg/wk, MAA 1.1 mmol/kg/wk and HAA 2.6 mmol/kg/wk (p<0.0001). In the HAA group plasma and urine K were significantly lower and non-oliguric hyperkaliemia was reduced. Discussion: Na homeostasis was very slight modified by early nutrition, suggesting that a negative Na balance is obligatory after birth. We showed that AA intake strongly affects K balance, minimize hyperkalemia and reduces weight loss. As K balance is strictly linked to cellular metabolism, we speculate that early nutrition may inhibit cellular catabolism and reduce the contraction of intracellular water compartment.