Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells via its spike protein, S1, binding to angiotensin-converting enzyme 2 (ACE2). Here, crossing of radiolabelled S1 (I-S1) into the brains of mice was shown to occur by adsorptive transcytosis and was increased by its co-injection with ACE2. Lipopolysaccharide-induced elevation of plasma cytokine levels, similar to that observed in some SARS-CoV-2 cases, also increased I-S1 brain entry and resulted in variable distribution across brain structures. Intranasally administered I-S1 was detected in all tested brain regions, especially the olfactory bulb and hypothalamus, but entered the brain with lower efficiency than systemically administered I-SI. This study supports a mechanism by which SARS-CoV-2 could enter the brain.