The current study aimed to characterize changes in EEG-related measures after noxious stimuli in neonates, and to assess their potential utility as measures of pain and/or discomfort during neonatal intensive care.Seventy-two healthy term infants were investigated: Twenty-eight had a non skin-breaking pin-prick on the heel, randomized to receive either oral glucose (n=16) or water (n=12) before the stimulus. 21 infants were studied during a venous blood sample from the dorsum of the hand, 23 infants during a capillary heel stick. Behavioral pain responses were assessed with the Premature Infant Pain Profile (PIPP) scale. The stimulus evoked a significant increase in higher frequency components (10-30Hz) which also correlated to behavioral measures. The frontotemporal localization of the increased activity with frequency bands similar to electromuscular artifacts and the relation to behavioral measures confirmed that this activity corresponds to an increase in muscle tone. There was no change in frontal EEG asymmetry in any of the groups. The present results indicate that responses in cortical activity recorded by EEG are not useful for clinical assessment of infants' responses to noxious stimuli.