This study investigates the types and degrees of physical and psychological discomfort experienced by hematopoietic stem cell donors before, during, and after the donation process in order to provide helpful information for developing education programs that can help donors to cope with their discomforts. One hundred and thirty-one individuals who donated hematopoietic stem cells from 2017 to 2019 were asked to self-report the types and degrees of physical and psychological discomfort they felt in the process, and the results were analyzed using SPSS. All participants donated peripheral blood stem cells; the most commonly reported physical discomfort was myalgia (72.5%), followed by bone pain (62.6%), fatigue (60.3%), and headache (55.0%). Of the donors, 88.5% responded that they experienced psychological discomforts, including fear (44.3%), anxiety (44.3%), stress (39.7%), depression (31.3%), loneliness (31.3%), regret (29.8%), and ambivalence (23.7%). In particular, female donors experienced more discomfort than males in rash (Z = -2.123, = 0.034), fear (Z = -2.851, = 0.004), and anxiety (Z = -1.861, = 0.044). Therefore, it is necessary for healthcare providers and experts to make efforts to educate and help donors to prepare and mitigate their discomfort throughout the donation process, and to strategically manage donors' well-being by monitoring and evaluating their discomfort levels and providing interventions if necessary.