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Abstract Infection of human cells by pathogens, including SARS‐CoV‐2, typically proceeds by cell surface binding to a crucial receptor. The primary receptor for SARS‐CoV‐2 is the angiotensin‐converting enzyme 2 (ACE2), yet new studies reveal the importance of additional extracellular co‐receptors that mediate binding and host cell invasion by SARS‐CoV‐2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens’ cellular uptake. Biophysical and cell infection studies are done to determine whether vimentin might bind SARS‐CoV‐2 and facilitate its uptake. Dynamic light scattering shows that vimentin binds to pseudovirus coated with the SARS‐CoV‐2 spike protein, and antibodies against vimentin block in vitro SARS‐CoV‐2 pseudovirus infection of ACE2‐expressing cells. The results are consistent with a model in which extracellular vimentin acts as a co‐receptor for SARS‐CoV‐2 spike protein with a binding affinity less than that of the spike protein with ACE2. Extracellular vimentin may thus serve as a critical component of the SARS‐CoV‐2 spike protein‐ACE2 complex in mediating SARS‐CoV‐2 cell entry, and vimentin‐targeting agents may yield new therapeutic strategies for preventing and slowing SARS‐CoV‐2 infection.