The emerging COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been raised as a global health challenge. Despite the breakthrough in the development of the COVID-19 vaccine, it still continues as a serious crisis, worldwide. The aberrant immune responses are strongly associated with the severity of the disease and an increased rate of morbidity and mortality among COVID-19 patients. The complement cascade activation is mediated by classical, lectin, and alternative pathways which could induce an inflammatory state during the COVID-19 infection. The growing body of research suggests that complement system activation plays an important role in the immunopathogenesis of SARS-CoV-2. Therefore, the blockade of complement cascades may be an effective approach to prevent the multi-organ complications of COVID-19. In this review, we will highlight the role of the complement system in the immunopathology of COVID-19, emphasizing the potential therapeutical targets to ameliorate COVID-19 infection.