BACKGROUND Sepsis in premature infants is associated with adverse neurodevelopmental outcomes. No previous studies have assessed acute changes in brain function during sepsis that might precede these adverse outcomes. METHODS We performed amplitude-integrated electroencephalography (aEEG) monthly, from 28 weeks until 36 weeks of postmenstrual age, on 108 premature infants born before 28 weeks of gestation. Additional aEEG recordings were performed during infants' first episode of sepsis. Two independent readers who were blinded to the infant's gestational age at birth and chronologic age, as well as to whether the infant had sepsis, evaluated aEEG recordings for the presence of burst suppression and assigned a maturation score. RESULTS Burst supression was found in 22% of aEEG recordings from infants without sepsis and 57% of recordings from infants with sepsis at the time of the recording (odds ratio=4.2; 95% confidence limits=2.4, 7.2; p<0.001). After adjustment for postmenstrual age at the time of the recording, the association between sepsis and burst suppression persisted (odds ratio=2.4; 95% confidence limits=1.2, 4.8; p=0.01). No statistically significant difference was found in the rate of increase in aEEG maturation score between infants with sepsis and those without. CONCLUSIONS Sepsis is associated with acute electroencephalographic changes, as indicated by burst supression, but not with a decreased rate of brain wave maturation.