Purpose: The purpose of this study was to explore factors affecting uncertainty and general well-being based on Uncertainty in Illness Theory. Methods: Data were collected from 125 outpatients who had received hemodialysis. The path model among four concepts, such as period of hemodialysis, social support, uncertainty, and general well-being, was tested. Tangible support, positive social interaction, affectionate, and emotional/informational support were measured as social support. Adaptation in the model was operationalized as general well-being which consisted of anxiety, depression, positive well-being, self-control, and general health. Results: All paths were statistically significant at the level of ${alpha}$=.05. The significant paths were the path from period of hemodialysis to uncertainty (t=-2.86), social support to uncertainty (t=-2.01), uncertainty to general wellbeing (t=-2.85), and social support to general well-being (t=3.55). Conclusion: Patients who perceived low uncertainty and high social support were likely to feel well-being. Therefore, nurses should give patients appropriate information according to their needs and have meaningful interaction with patients to reduce their uncertainty and render social support.