In Coronavirus Disease 2019 (COVID-19), the initial viral-replication phase is often followed by a hyperinflammatory reaction in the lungs and other organ systems ('cytokine storm') that leads to acute respiratory distress syndrome (ARDS), multi-organ failure, and death despite maximal supportive care. Preventing hyperinflammation is key to avoiding this progression to severe stages of COVID-19. We have previously demonstrated that alpha-1 adrenergic receptor (1-AR) antagonists can prevent cytokine storms and resulting death in mice. Here we present a retrospective study of outcomes in patients with ARDS (n = 13,125) or pneumonia (n = 108,956). Patients who were taking 1-AR antagonists for other conditions had lower probability of needing invasive mechanical ventilation and dying in the hospital compared to non-users, both in ARDS (adjusted OR = 0.59, 95% CI 0.34-0.95, p = 0.021) and in pneumonia (adjusted OR = 0.77, 95% CI 0.62-0.94, p = 0.007). By contrast, no significant effect was observed for beta-adrenergic receptor (-AR) antagonists. These results support the study of 1-AR antagonists for reducing mortality in pneumonia and ARDS and highlight the need for prospective trials of 1-AR antagonists to assess their efficacy in preventing cytokine storm and death in COVID-19.