This study investigated the characteristics of inflammatory and immune changes in patients with severe intracranial infection and examined their correlation with prognosis. Methods: We reviewed the clinical data of 62 patients with severe intracranial infection admitted to the neurological intensive care unit of our hospital from December 2018 to December 2019. General demographic information, diagnosis and treatment, inflammatory indicators, immune function indicators, and prognosis were collected for statistical analysis. Results: These 62 patients had a median lowest Glasgow coma scale (GCS) score of 9 (IQR: 6-12); 30 (48.4%) received mechanical ventilation; in-hospital mortality rate was 4.8%. Among the inflammatory indicators, white blood cell count, neutrophil count, hypersensitive C-reactive protein (hs-CRP), procalcitonin (PCT), erythrocyte sedimentation rate, IL-2 receptor, IL-6, and TNF-α were all higher than normal while lymphocyte count was lower than normal. Among the cellular immunity indicators, the total T lymphocyte, CD4+ T cell, CD8+ T cell, and NK cell counts were significantly below the normal range. Patients with severe unconsciousness (GCS score ≤8) had significantly increased mechanical ventilation rates, hospital mortality, and hs-CRP levels. Patients who accepted mechanical ventilation had significantly lower GCS scores and significantly higher neutrophil counts and hs-CRP and procalcitonin levels. Conclusion: Patients with severe intracranial infection showed significant increases in inflammatory indicators and significant abnormalities in cellular immunity indicators. To some extent, inflammatory indicators such as hs-CRP are correlated with the severity and prognosis of patients with severe intracranial infection.