Caffeine is commonly consumed in an effort to enhance speed in performance and wakefulness. However, little is known about the deleterious effects it can produce on the brain, this study aimed at determining the extents of effects and damage that can be caused by excessive consumption of caffeine on the cerebral cortex of mice models with a view to examining caffeine effects on cerebral cortex histoarchitecture and cell morphologies. Twenty adult mice were used for this study. They were randomly divided into 4 groups of 5 animals each. Control rats were administered normal saline, experimental groups received caffeine through oral cannula at 10, 50 and 120 mg/kg body weight for 28 days to determine effects of graded doses of caffeine administration. The dosage of the caffeine selection was based on previously published work. The result indicates that at low and medium doses of caffeine administration, features of prominent eosinophilic cytoplasm with or without shrunken nuclei was observed in plates 1B, 1C, and 3B, 3C. And at high dose, features of degenerating neurons such as pyknotic nuclei and sparse neuronal population were observed in plates 2D and 3D when compared to the normal appearance of the neurons and the glial cells. In conclusion, low and medium doses of caffeine induced mild changes in cortical neuron morphology and at higher dose of caffeine administration, neurodegenerative changes were observed in cerebral histoarchitecture. This shows that at high dose, caffeine consumption can produce detrimental effects on brain structure as well as function in adult mice models.