PARP14 and PARP9 play a key role in macrophage immune regulation. SARS‐CoV‐2 is an emerging viral disease that triggers hyper‐inflammation known as a cytokine storm. In this study, using in silico tools, we hypothesize about the immunological phenomena of molecular mimicry between SARS‐CoV‐2 Nsp3 and the human PARP14 and PARP9. The results showed an epitope of SARS‐CoV‐2 Nsp3 protein that contains consensus sequences for both human PARP14 and PARP9 that are antigens for MHC Classes 1 and 2, which can potentially induce an immune response against human PARP14 and PARP9; while its depletion causes a hyper‐inflammatory state in SARS‐CoV‐2 patients.