Pneumococcal meningitis is characterized by a severe inflammatory reaction in the subarachnoid and ventricular space of the brain, disruption of the blood-brain barrier, hearing loss, and neurologic sequelae in as many as 27% of surviving patients. Several experimental studies have shown that erythropoietin (EPO) and its receptor are expressed in the central nervous system and have neuroprotective properties through the inhibition of apoptosis, as well as anti-inflammatory, antioxidant, angiogenic, and neurotrophic effects. In the current study, we demonstrated the effect of erythropoietin (EPO) on lipid peroxidation, protein carbonylation, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), and behavioral parameters in rats with pneumococcal meningitis. EPO decreased lipid peroxidation and protein carbonylation, and it prevented protein degradation in the hippocampus and frontal cortex. MPO activity was decreased, and both SOD and CAT activity were increased in the first 6 hours after pneumococcal meningitis induction. Novel object recognition memory was impaired in the meningitis group; however, adjuvant treatment with EPO prevented memory impairment during both the short- and long-term retention tests. The meningitis group showed no difference in motor and exploratory activity between training and test sessions in the open-field task, which indicates that habituation memory was impaired; however, adjuvant treatment with EPO prevented habituation memory impairment. Although there are some limitations with respect to the animal model of pneumococcal meningitis, this study suggests that adjuvant treatment with EPO contributed to decreased oxidative stress and prevented cognitive impairment.