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Reports that sweet taste calms crying in newborns and is analgesic against the pain caused by a heel lance served as the basis for this study. Electroencephalographic (EEG) activity, heart rate activity, and infants’ facial behaviors were recorded before and after a noninvasive, but noxious, heelstroke (procedure from the Brazelton Neonatal Behavior Assessment Scale). In a randomized and controlled trial, 34 newborns were administered 2 mL of water or sucrose solution before the heelstroke. Frontal EEG asymmetry scores were computed, and power in the 3 to 6 Hz frequency band was analyzed. Infants who received water showed increased relative right frontal EEG activation from baseline to the post-heelstroke phase, a pattern that typifies negative affect. The EEG of infants in the sucrose group did not change. Heart rate increased rapidly in both groups during the heelstroke phase. However, after the heelstroke, the heart rate of infants who received sucrose returned to baseline, whereas the heart rate of infants who tasted water remained elevated. During the heelstroke, the infants in the water group cried and grimaced twice as long as the infants in the sucrose group. These findings add to the growing literature showing that sucrose attenuates newborns’ negative response to aversive or noxious stimuli.