Background: Health self-efficacy acts as a vital mediator in the causal pathway from awareness of self-management to self-care behaviors. However, little is known about the underlying predictors of this concept. Purpose: Guided by existing theories and models, this study tested the effects of patient-centered communication, emotional well-being, confidence in health information-seeking, and future time perspective on individuals' perceived efficacy in managing health. Methods: Data from Cycle 3 of HINTS 5 (n= 3239) were examined through hierarchical ordinary least squares (OLS) regression analysis. Results: All these four variables were found to have significant positive associations with health self-efficacy. In particular, emotional well-being and confidence in seeking health information had the highest size effect. Discussion: The findings enrich the existing literature by identifying the four potential determinants of self-efficacy in managing health. Translation to Health Education Practice: Several implications for health education and promotion can be drawn. First, there is a need for Health Educators to implement interventions aimed at promoting patient activation and offering easy access to high-quality health knowledge. Second, Certified Health Education Specialists should design more tailored and culturally appropriate health promotion programs to help individuals exercise human agency, establish long-term goals, and keep a positive mind-set.