Objectives: Immune perturbation induced by tumor burden has been showed as the hallmark of brain tumors. To date, the vast majority of studies have focused heavily on local immune responses in the tumor microenvironment. Little is known about how the systemic immune macroenvironment is modulated by neurosurgical tumor resection in patients with brain tumors. Method: Medical records from patients with brain tumors admitted to the Department of Neurosurgery at the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences between January 2021 and March 2022 were retrospectively reviewed. Forty-nine patients who have lymphocyte subsets, serum immunoglobulins, C-reactive protein, and complements levels before neurosurgical tumor resection and at least once test after surgery were included into the final analysis. Results: Postoperative CD3+ lymphocytes, CD4+ lymphocytes and CD4+/CD8+ lymphocyte ratio presented bi-phasic changes, which indicated an initial decrease and a subsequent increase after neurosurgical tumor resection. Moreover, neurosurgical tumor resection induced a decrease in natural killer lymphocytes and an increase in B lymphocytes that persisted through the entire observation period after surgery. Meanwhile, significant changes in humoral immunity characterized by a decrease in immunoglobulins (IgA, IgG, and IgM) levels and an increase in the CRP level occurred after neurosurgical tumor resection. In addition, patients with postoperative infection complication had a lower preoperative CD4+/CD8+ lymphocyte ratio. Conclusions: These findings provide evidence that either cellular immunity or humoral immunity can be remodeled by neurosurgical tumor resection, and patients with disturbed systemic immunity have increased risk of infection after surgery.