['Hyperglycaemia is a common complication of prematurity and is associated with neonatal mortality and morbidity, yet the aetiology is incompletely understood. C-peptide has been used in adults to estimate endogenous insulin secretion due to its simple clearance kinetics.', 'To determine insulin secretion calculated from plasma C-peptide concentrations in hyperglycaemic preterm babies.', 'This is a retrospective analysis of a cohort of 41 very preterm babies with a median gestational age of 27.2 weeks (26.2-28.7) enrolled in a randomised controlled trial of tight glycaemic control when they developed hyperglycaemia (2 consecutive blood glucose concentrations, BGC, > 8.5 mmol·l(-1)). Insulin secretion was determined using a steady state analysis of a 2-compartment C-peptide kinetic model.', 'BGC, plasma insulin concentration, plasma C-peptide concentrations, and insulin secretion were higher at randomisation than 1-2 weeks following randomisation (p ≤ 0.02). Insulin secretion was higher in girls at 11.7 mU·l(-1)·kg(-1)·min(-1) (5.3-18.7) vs. 4.7 mU·l(-1)·kg(-1)·min(-1) (2.1-8.3; p < 0.005), with no difference in clinical characteristics, BGC, plasma insulin concentration, or nutrition between the sexes (p > 0.25). Insulin secretion was lower in samples taken during exogenous insulin delivery at 3.7 mU·l(-1)·kg(-1)·min(-1) (1.8-6.9) vs. 9.8 mU·l(-1)·kg(-1)·min(-1) (4.7-17.8; p = 0.02).'] Do hyperglycaemic Preterm Babies Have Sex Differences in Insulin Secretion?