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As a healthcare ICT4D solution, mobile health (mHealth) can potentially improve users' well‐being during pandemics, especially in developing countries with limited healthcare resources. Recent ICT4D research reveals that providing end‐users with access to ICT is insufficient for improving well‐being and, thus, understanding how mHealth empowers end‐users to enhance well‐being against stressful events is important. However, prior research has rarely discussed the issue of empowerment in the domain of mHealth or the context of major disruptive events. This paper contributes to the literature by conceptualizing the psychological empowerment of mHealth users (PEMU) and investigating its nomological network during pandemics. Drawing upon theories of psychological empowerment and event characteristics, we developed a research model and tested it through a mixed‐methods investigation, containing a quantitative study with 602 Chinese mHealth users during COVID‐19 and a follow‐up qualitative study of 326 online articles and reviews. We found that PEMU, driven by three technological characteristics (perceived response efficacy, ease of use, and mHealth quality), affects well‐being through both (a) a stress‐buffering effect, which counterbalances the detrimental, stress‐increasing effects of event criticality and disruption, and (b) a vitality‐stimulating effect, which is intensified by event criticality. These findings have important implications for ICT4D research and practice. [ABSTRACT FROM AUTHOR]