The current comparative study sought to identify psychosocial stressors of corona-virus disease 2019 (COVID-19)-dedicated (n = 110) and non-COVID-19-dedicated (n = 118) nurses (herein referred to as COVID nurses and non-COVID nurses, respectively). Data were collected online from October 20, 2020, to April 1, 2021. Significant predictors of mental health for COVID nurses were purpose/meaning (β = -0.32, p < 0.001), perceived stigma (β = 0.25, p = 0.001), perceived work environment improvement (β = -0.22, p = 0.004), and absolute work intensity (β = 0.26, p = 0.004). For non-COVID nurses, predictors were purpose/meaning (β = -0.34, p < 0.001) and absolute work intensity (β = 0.26, p = 0.003). It is necessary to develop programs and policies that support the mental health of nursing staff. Administrative efforts should be made to create a work environment that allows nurses to focus on their work during health crises, such as the COVID-19 pandemic. Nursing staff should be supported so that appropriate working hours are maintained and breaks are guaranteed. [Journal of Psychosocial Nursing and Mental Health Services, 61(1), 39-46.].