ABSTRACT During the prolonged COVID-19 pandemic, health communication researchers and practitioners should be aware of the unintended effects of message fatigue. Message fatigue is a motivational state caused by repeated and prolonged exposure to similar health-related messages that induces resistance to health behaviors. Messages encouraging COVID-19 vaccination tend to focus on scientific evidence and efficacy information. However, prolonged exposure to similarly framed repeated pro-COVID-19 vaccination messages may cause message fatigue, generate psychological reactance, and lead to ineffective persuasive outcomes. Scholars of message fatigue argue that health communication practitioners should select a less common frame to reduce fatigue responses and increase favorable attitudes toward message recommendations. Entering the second year since COVID-19 vaccination has begun, to reduce message fatigue, future pro-COVID-19 vaccination communication should increase the diversity of messages different than the frequently used types. This opinion piece proposes alternative dissemination of cognitive, affective, narrative, and non-narrative pro-COVID-19 vaccination messages.