β-Hydroxybutyrate (3HB) is a small molecule produced as a ketone body in mammalian animals. It has been found that 3HB provides not only energy for a body, it also participates in cell signal transduction events as a signal molecule. This study focuses on investigation of 3HB immunomodulatory mechanisms. Proteomic analysis indicates a new post-translational modification of β-hydroxybutyrylation (Kbhb) on antibodies. Because of the low level of Kbhb antibodies and the associated difficulty in purifying them, simulated Kbhb antibody was produced using chemical modification . The chemically modified Kbhb antibody was shown to improve the stability of antibodies to protease and heat treatments. Furthermore, Kbhb of antibodies stabilizes the antibodies in plasma. As a remarkable example, COVID-19 neutralizing antibody B38 produced by 293T cells was Kbhb modified and stabilized , providing a strategy for the possibility of extending the protection effects of COVID-19 antibodies.