Aim: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. Methods: We performed a case- control study on neonates with birthweight less than 1250 g admitted to our tertiary- level unit during the years 1998- 2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late- onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Results: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6% ) than in group B neonates (11/46, 23.9% ) (OR 1.95, 95% CI 1.235- 4.432, p = 0.008). Moreover, in 19 of 21 (90.4% ) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Conclusions: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late- onset sepsis, with a typical 3- d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur. Aim: The incidence of invasive fungal infection in preterm newborns is rising steadily. But early diagnosis and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. Methods: We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998- 2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (serum glycaemia> 215 mg / dl, ie 12 mmol / l) in the first month of life, and its temporal relationship with the episodes of sepsis. Results: Hyperg lycaemia significantly more in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235- 4.432, p = 0.008) 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episomally occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Conclusions: Hyperglycaemia is significantly more frequent in neonates who- - onset sepsis, with a typical 3- d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be of carefully evaluated for systemic fungal infection whenever signs of carbohydrateintolerance occur.