NK cells and diverse populations of unconventional T cells, such as MAIT cells, gammadelta T cells, invariant NKT cells, and DNTabeta cells are important early effector lymphocytes. While some of these cells, such as NK cell and MAIT cells, have well-established roles in antiviral defense, the function of other populations remains more elusive. Here, we summarize and discuss current knowledge on NK cell and unconventional T cell responses to SARS-CoV-2 infection. Also covered is the role of these cells in the pathogenesis of severe COVID-19. Understanding the early, both systemic and local (lung), effector lymphocyte response in this novel disease will likely aid ongoing efforts to combat the pandemic.