Improving health literacy, acculturation, eHealth use, and patient activation among Mexican Americans has the potential to improve their quality of life, access to care, and reduce costs associated with healthcare. However, health literacy and patient activation levels remain low among the Mexican American population. Identifying whether a relationship exists between health literacy, eHealth use, acculturation, and patient activation among Mexican Americans can assist healthcare organizations and policy makers with identifying, developing, and implementing programs and policies that can improve health literacy, eHealth use, acculturation, and patient activation within this vulnerable population. This study investigated patient activation among Mexican Americans in order to identify if an individual’s degree of health literacy, eHealth use, and acculturation effects patient activation among Mexican Americans. Results showed a significant negative correlation was identified between health literacy using the Single Item Literacy Screener (SILS) and patient activation measure (PAM) (r_p = -0.24, p < .001), eHealth use (EHEALS) significantly predicted patient activation (PAM), B = 8.63, t (193) = 5.92, p < .001 and no correlation was identified between the PAM and the Short Acculturation Scale for Hispanics (SASH) among Mexican Americans.