The current study investigated the psychological well-being and coping mechanisms of care home staff during the coronavirus disease 2019 (COVID-19) lockdown. Among 147 staff members, 21.8%, 24.5%, and 12.9% reported depression, anxiety, and stress, respectively. The results of structural equation modeling showed that self-efficacy and coping strategies had direct effects on psychological well-being. In the paths from self-perceived caregiving to psychological well-being, self-efficacy and positive coping strategies played mediating roles independently and together, and social support played a mediating role together with coping strategies. Care home staff's psychological well-being was undermined during the COVID-19 lockdown. Interventions aimed at improving staff's self-efficacy, adoption of positive coping strategies, and avoidance of negative coping strategies or considerations of social support along with coping strategies are suggested to decrease exhibited symptoms of depression, anxiety, and stress. [Research in Gerontological Nursing, 14(4), 180-190.].