Purpose The relationship between uncertainty and self-care behaviors is well documented in the literature, however, there exists a paucity of information on the mediating effect of perceived stress on the relationship between uncertainty and self-care ability among enterostomy patients. This study aimed to examine the relationship between uncertainty and self-care ability among enterostomy patients, and explore the mediating role of perceived stress.Methods 462 enterostomy patients aged (60.00 ± 12.81) years old participated in the study. Cross-sectional study was conducted among them by a set of self-administered questionnaires, which includes demographic information, perceived stress scale, illness uncertainty scale, and ostomy self-care ability scale. Multiple linear regression analyses were performed to explore the role of perceived stress between Uncertainty and self-care ability, structural equation modeling was used to verify it.Results 450 participants finally completely finished the research, with the recycling rate of 97.4%. Uncertainty was demonstrated positively related to perceived stress(r = 0.215, P < 0.01), and negatively related to self-care ability(r=-0.470, P < 0.01), perceived stress was negatively related to self-care ability(r=-0.640, P < 0.01). Perceived stress played a partially mediating role between Uncertainty and self-care ability, which accounted 40.8 % of the total effect.Conclusions The findings present a conceptual model containing the mediated effects of perceived stress, which facilitated our understanding of the relationship among uncertainty, perceived stress, and self-care ability. Thus, perceived stress and uncertainty should be the focus, in order to improve self-care ability of the enterostomy patients.