The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) devastation on the central nervous system (CNS) is ascertained by the present clinical findings and the noticeable signs and symptoms. The CNS involvement of the virus is not trivial; although the brain has highly protective systems, the virus has ways to breach them with a destructive potential. For successful entry of the virus, different possible routes with favorable mechanisms are used. The SARS-CoV-2 invasion induces a mechanism of both the innate and adaptive immune response to control virus replication and removal from the CNS tissues. The cytokine storm and autoimmune response during the immunological events result in demyelination, damage of resident cells and neurons, cerebrovascular thrombosis, and dysregulation of neuro signaling pathways. Furthermore, hypoxia and toxemia accelerate the neurological destruction process. The acute attributions on psychology due to inflammation is a hallmark of CNS involved pathogenesis; nevertheless, the productivity, durability, and longevity of virus-specific lymphocytes are the vital indicators for complete removal of viral antigen and in combat against reinfection of the CNS. Keywords: CNS invasion; immune response; cytokine storm; demyelination; mental status.