Student well-being has emerged as a topic of considerable interest to researchers and educators. Recent work has sought to examine relationships between measures of student well-being and other constructs such as academic achievement, physical health, relationships with peers, and engagement in learning. Reading assessment and context questionnaire data available through PIRLS 2021 can be used to add to these conversations. This report begins with a brief discussion of relevant research literature—including how student well-being is defined, as well as the relationships between well-being and other factors of interest. PIRLS 2021 was not designed to measure student well-being explicitly and does not provide a comprehensive well-being measure. However, the PIRLS 2021 Student Questionnaire collected data for several measures that can serve as indicators for this complex construct (see PIRLS 2021 Context Questionnaire Framework). This report presents these indicators and their relationships to students’ reading achievement. The results are discussed in light of existing research on student well-being, as well as factors unique to PIRLS 2021. These discussions form the basis for a more complex analysis that integrates the individual indicators to describe multidimensional profiles related to students’ well-being. The report concludes with key findings and directions for further exploration of student well-being in future cycles of PIRLS.