Caffeine is widely used for the treatment of apnea in premature neonates. However, the localization of caffeine's target site (central nervous system and/or peripheral chemoreceptors) is not well defined, especially for sleeping neonates whose sleep stages interact with respiratory control. The aim of this study was to assess the activity of the peripheral chemoreceptors in relation to sleep stages in premature neonates treated (or not) with caffeine for idiopathic apnea. Peripheral chemoreceptor activity was assessed in 22 neonates (postconceptional age of 36 ±1 weeks with birth weights ranging from 790 to 1910 g) by performing a 30sec hyperoxic test during active and quiet sleep. Eleven neonates received caffeine treatment (4,0 ±0,5 mg.Kg^-1.day^-1) and 11 served as controls. For all neonates, the decrease in minute ventilation observed during hyperoxia was greater during active than during quiet sleep. Neonates receiving caffeine showed a significantly greater decrease in ventilation during hyperoxia in both sleep stages, compared to controls (caffeine; -29.7 ±12.8% vs control; -22.0 ±7.4%; F_1,15 = 4.6, p = 0.04). We conclude that caffeine administration increases the effectiveness of chemoreceptor activity. Since sleep stage durations were not affected by the treatment, it is likely that the decrease in apneic episodes typically observed with caffeine therapy is only related to respiratory processes, and is independent of the sleep stage organization.