Introduction: The community health agent plays an essential role as a link between the community and health institutions; the effectiveness of their work is crucial in promoting health, prevention, and detection of diseases. Motivation and empowerment could affect the performance of the community agent in carrying out his work. Objective: To determine if work motivation and empowerment are factors associated with the self-efficacy of the community health agent. Methodology: Observational and cross-sectional study. The study included community health agents in the Non-Governmental Organization ADRA in Imbabura and Pichincha, Ecuador. The sample selected by the census method corresponds to 300 agents. The instruments were the Motivation at Work Scale (R-MAWS), the Psychological Empowerment Scale, and the Professional Self-efficacy Questionnaire (AU10). Descriptive statistical analyses were performed using dispersion and summary measures—a comparative analysis with chi-square. The inferential analysis was done through logistic regression where the B coefficient and the odds ratio (OR) with 95% confidence intervals (CI) were evaluated, P < .05. The theoretical and adjusted model of the structural model allowed us to corroborate the association of the variables. Results: Motivation had a positive effect on self-efficacy (OR = 10.091, CI [5.509-18.485], P < .05), empowerment had a minimal effect (OR = 0.664, CI [0.363-1.214], P > .05), which is not significant to predict the perception of self-efficacy. Conclusion: This study suggests that to improve the self-efficacy of the work of community health agents, it is necessary to intervene through strategies that keep them motivated in the exercise of their mediation work between the community and health institutions. Likewise, empowering them would contribute to self-efficacy and thus help in the fulfillment of the functions of health agents.