ABSTRACT Background Evidence-based health communication is crucial for facilitating vaccine-related knowledge and addressing vaccine hesitancy. To that end, it is important to understand the discourses about COVID-19 vaccination and attend to the publics’ emotions underlying those discourses. Methods We collect tweets related to COVID-19 vaccines from March 2020 to March 2021. In total, 304,292 tweets from 134,015 users are collected. We conduct a Latent Dirichlet Allocation (LDA) modeling analysis and a sentiment analysis to analyze the discourse themes and sentiments. Results This study identifies seven themes of COVID-19 vaccine-related discourses. Vaccine advocacy (24.82%) is the most widely discussed topic about COVID-19 vaccines, followed by vaccine hesitancy (22.29%), vaccine rollout (12.99%), vaccine facts (12.61%), recognition for healthcare workers (12.47%), vaccine side effects (10.07%), and vaccine policies (4.75%). Trust is the most salient emotion associated with COVID-19 vaccine discourses, followed by anticipation, fear, joy, sadness, anger, surprise, and disgust. Among the seven topics, vaccine advocacy tweets are most likely to receive likes and comments, and vaccine fact tweets are most likely to receive retweets. Conclusions When talking about vaccines, publics’ emotions are dominated by trust and anticipation, yet mixed with fear and sadness. Although tweets about vaccine hesitancy are prevalent on Twitter, those messages receive fewer likes and comments than vaccine advocacy messages. Over time, tweets about vaccine advocacy and vaccine facts become more dominant whereas tweets about vaccine hesitancy become less dominant among COVID-19 vaccine discourses, suggesting that publics become more confident about COVID-19 vaccines as they obtain more information.