Infants have strong cortical responses to a noxious stimulus from 28 weeks postmenstrual age (PMA), however, the cortical substrate required for nociceptive processing undergoes dramatic changes over the equivalent of the last trimester of gestation and increases in complexity potentially with a sexually dimorphic trajectory. In this study, we aim to map the functional development in the serial cortical processing of a clinically required noxious procedure in male and female preterm and term neonates over the equivalent of the last trimester of gestation.