Cortical spreading depression (CSD) is influenced by brain excitability and is related to neurological diseases, such as epilepsy. In vitro evidence indicates that neuronal electrical activity is potentiated after CSD. Malnutrition can cause electrophysiological changes in the brain, both in animals and in humans. Here, we investigated in vivo whether CSD potentiates the amplitude of electrocorticogram (ECoG) and of transcallosal evoked responses in adult well-nourished (W), early-malnourished (M), and food-restricted rats. ECoG amplitudes were compared before and after CSD, at two parietal regions (designated the anterior and posterior regions). In the anterior region, post-CSD amplitudes of the ECoG waves were 13-23% higher (P < 0.05) than the pre-CSD values in all groups. In the posterior region, amplitudes increased 22% in the M group only (P < 0.05). In a fourth CSD-free group, ECoG amplitude did not change during the four recording hours. Transcallosal electrically evoked cortical responses also increased 21.5 ± 9.6% and 41.8 ± 28.5%, after CSD, in the W and M conditions, respectively, as compared to pre-CSD values. The data support the hypothesis of an in vivo CSD potentiation on cortical excitability as recorded by spontaneous and evoked electrical activity and modulation by nutritional status.