Background: Protection motivation to practice preventive behaviors is necessary for sustained mitigation during coronavirus disease 2019 (COVID-19); however, limited research exists on the ecological sources of influence for COVID-19 protection motivation. Aim: To explore sources of influence (family health, media consumption, and loss of work hours) on COVID-19 protection motivation. Method: An online quantitative survey of U.S. adults (N = 501) aged 18 years or older was administered using Qualtrics with participants recruited through Amazon Mechanical Turk. Data were collected on constructs related to the protection motivation theory and theory of planned behavior as well as sources of influence and intention to socially distance and socially isolate during COVID-19. Constructs were further defined through exploratory and confirmatory factor analyses. Structural equation modeling was used to determine relationships between constructs. Results: A two-factor model was identified with threat appraisal as one factor and subjective norms appraisal, coping appraisal, and behavioral intention loading as another factor. Higher news media consumption and loss of work hours due to COVID-19 were both significant predictors of increased threat appraisal. Family healthy lifestyle and family health resources were significantly related to increases in the subjective norms, coping appraisal, and behavioral intention appraisal factor. Conclusions: Family health, news media consumption, and loss of work hours are associated with COVID-19 protection motivation. COVID-19 protection motivation might be enhanced through policies and messaging that can affect ecological sources of influence.