In order to research the relationship between neurological sequelae of COVID-19 and acetylation of brain cortexes, we reported for the first time the acetylome in the brain cortex of the K18-hACE2 infected mouse model, and the difference between the SARS-CoV-2 infection group and the control group, which found the largest amount of acetylated proteins in the brain cortex of the mouse to date, greatly expanding the existing database of acetylome. Besides, it would also lay a foundation for the subsequent research on the pathogenesis and treatment of COVID-19 patients.