Natural killer (NK) cells play an important role in antiviral resistance. The integrin α2 (α2), which dimerizes with integrin β1 (β1), distinguishes NK cells from Innate Lymphoid Cells 1 (ILC1) and other leukocytes. Despite its use as an NK cell marker, little is known about the role of α2β1 in NK cell biology. Here we show that in mice, α2β1 deficiency does not alter the balance of NK cell/ILC1 generation, and slightly decrease the number of NK cells in the bone marrow and spleen without affecting NK cell maturation. NK cells deficient in α2β1 had no impairment at entering or distributing within the draining lymph node (dLN) of ectromelia virus (ECTV) infected mice or at becoming effectors, but proliferated poorly in response to ECTV and did not increase in numbers following infection with mouse cytomegalovirus (MCMV). Still, α2β1 deficient NK cells efficiently protected from lethal mousepox and controlled MCMV titers in the spleen. Thus, α2β1 is required for optimal NK cell proliferation but is dispensable for protection against ECTV and MCMV, two well established models of viral infection where NK cells are known to be important.