Very preterm (VPT) infants are exposed to odors released by healthcare products, triggering the trigeminal and olfactory subsystems. Irritation of the nasal mucosa induces pain in adults. We examined whether preterm and full-term (FT) newborns perceived trigeminal odors at different cortical levels, whether these odors elicit pain, and if oral glucose modulates this pain. We performed 44 recording sessions in newborn (15 VPT infants, 12 VPT infants at term-equivalent age, and 17 FT infants) following exposure to trigeminal/olfactory stimuli from the hospital environment. We repeated the exposure after oral glucose administration. We recorded cortical activation in the olfactory, frontal, and somatosensory cortices by functional near-infrared spectroscopy, and analyzed pain behaviors from videotaped recordings. Newborns integrated trigeminal/olfactory stimuli in trigeminal/olfactory and nociceptive processing areas beginning at 31 weeks postmenstrual age, and also exhibited pain behaviors. Pain scores were positively associated with the level of cortical activation. Oral glucose inhibited pain behaviors and cortical activation. There were developmental differences in cortical integration related to brain maturation and duration of the extra-uterine experience. In conclusion, VPT and FT infants showed trigeminal sensitivity after exposure to alien odors that induce pain, potentially affecting the wiring of the neuronal circuits of the newborn brain.