This preprint explores the ability of SARS-CoV-2 to infect and replicate in neural tissues of mouse and human origin. Induced pluripotent stem cell lines derived from healthy donors were used to generate human brain organoids for modelling SARS-CoV-2 infection. Extensive cell death and metabolic changes occurred in both infected and neighbouring neurons, inducing locally hypoxic regions with no evidence of a type I interferon response. Organoids incubated with antibodies to ACE2 or to viral spike protein from the cerebrospinal fluid of patients with COVID-19 had decreased SARS-CoV-2 infection. Transgenic mice overexpressing human ACE2 (hACE2) in the brain had decreased survival after SARS-CoV-2 infection compared with those expressing hACE2 in lungs. This study provides insight into the neuroinvasive potential of SARS-CoV-2, which could explain neurological symptoms experienced by some patients.