Erythropoietin (EPO) and its receptor are expressed in the brain, and one of its roles appears to be neuroprotection. This study investigates whether chronic overexpression of EPO changes brain mRNA expression in the brains of transgenic mice. Therefore, cerebral mRNA expression was investigated in transgenic mice overexpressing EPO. Microarray analysis revealed an upregulation (2.8- to 3.6-fold) of N-acetylglucosamine-6-O-sulfotransferase (prolongation of the EPO effect), a translocase of the inner mitochondrial membrane (mitochondrial matrix import of nuclear encoded proteins), a mitochondrial ribosomal protein (mitochondrial protein translation), and a peroxisomal biogenesis factor (formation of peroxisomes). In conclusion, components of oxidative metabolism pathways were activated at the level of transcription which could be related to neuroprotective effects of EPO or could indicate compromised tissue.