The nursing discipline has focused on uncertainty as a main theme of research as well as an area needing assessment in clinical practice because the concept of uncertainty can be applied across diagnostic categories and may be worthwhile in explaining responses to illness. This study aimed to examine the effects of uncertainty on perceived health status including physical health, mental health, and general health within the theoretical framework of uncertainty in illness. This descriptive correlational and cross-sectional survey study included 81 subjects with atrial fibrillation using a face-to-face interview method. Individuals with greater symptom severity perceived more uncertainty and uncertainty was appraised as a danger rather than opportunity, thus those with greater uncertainty appraised a greater danger. While there was no relationship between danger appraisal and physical health, the significant relationships were shown between danger appraisal and mental health (r = -0.68) and between danger appraisal and general health (r = -0.39) respectively. The symptom severity had a significant direct effect on general health rather than having indirect effects through uncertainty and appraisal. Uncertainty had a significant impact on the perception of mental health through danger appraisal, identifying an area for nursing interventions. The mediating model of uncertainty with mental health as an outcome variable was supported by the empirical data of this study. In order to expand the present body of knowledge on uncertainty in illness model, recommendations for the future nursing studies and nursing practice were included.