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Brain abscesses most frequently occur because of bacterial dissemination from a primary lesion at a distant site or direct contiguous invasion from an adjacent site of infection. We examined serum and saliva cytokine levels in a brain abscess patient with severe periodontitis. A 66-year-old man with high-grade fever and right-sided paresis was hospitalized. Brain magnetic resonance imaging (MRI) revealed several nodules in his right parietal and occipital lobes. We also found increased leukocyte (10,532/ml) and cerebrospinal fluid white blood cell (235–7860 mm³) counts. Bacteriological examination of sputum showed Fusobacterium nucleatum and Prevotella. No ear, nose, throat, and gastrointestinal infections were observed. Severe periodontitis was noted. Bacteriological examination of the right maxilla showed Porphyromonas gingivalis, and we detected a high level of serum antibody to P. gingivalis. Broad-spectrum antimicrobial therapy, dental calculus removal, and intraoral remediation improved the patient’s general condition. Brain MRI at the time of discharge showed a decrease in the size of the nodules, and after three months, the level of serum antibody to P. gingivalis decreased. Elevated pro-inflammatory cytokines such as interleukin (IL)-1α and IL-1β and chemokines such as IL-8, macrophage chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF), and vascular endothelial growth factor (VEGF) levels in the saliva significantly decreased after oral treatment. Similarly, elevated serum IL-1α, IL-1β, IL-8, MCP-1, eotaxin, regulated on activation, normal T-cell expressed and secreted (RANTES), VEGF, and tumor necrosis factor-alpha (TNF)-α levels decreased after oral treatment. These findings supported our hypothesis that periodontopathic bacteria produce inflammation cytokines, pro-inflammatory cytokines migrate from systemic circulation to the brain, and their expression increases, and transition of that response into an adaptive form might have been the etiology of brain abscess in our patient.