Within the context of the broad application of online teaching and learning during the COVID-19 pandemic, this chapter aims to explore two questions: What are the well-being challenges for Hong Kong university students in online learning during the pandemic? And what are university students’ responses to these challenges? This chapter is based on a quantitative analysis of the well-being-related survey data collected from 1227 Hong Kong university students. From the perspective of well-being, this chapter finds that the sudden transformation to online learning has brought many issues related to Hong Kong university students’ physical (like eye fatigue) and psychological (like increased stress) status. These issues have been augmented by the compact living situation of some university students from low-income families in Hong Kong. This chapter proposes that higher education institutions and instructors should ensure students’ physical and psychological well-being through course restructuring (e.g., scheduling frequent breaks and applying interactive tools to increase student engagement) and relevant professional development programs for instructors (e.g., online platform training and online course design and delivery). Copyright © 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG.