Even under the best of circumstances, employee health and well-being in South African universities, especially for academics, is a major cause of concern. Attributable to this, for example, are both physical and mental health problems arising from the pressure that comes with expectations to concurrently fulfill performativity targets in areas such as teaching, research, and community service. The COVID-19 pandemic aggravated this situation with the closure of universities and the switch to online teaching and learning as a result of which some academics experienced challenges in terms of the use of technology for teaching the cost of gadgets such as laptops and smart phones and non-participation in online classes by some students. In addition, some of the academics were affected by the social isolation and disconnectedness from colleagues caused by working from home. Using critical realism, and drawing some insights from social realism, this conceptual chapter suggests a framework on the basis of which the health and well-being of academics could have been re-imagined during the COVID-19 pandemic. Among other suggestions, the framework advocates that the health and well-being of academics at South African universities should be looked at as a layered phenomenon whose form is a function of the complex interactions among multiple agents found in different structural contexts. Insights from this framework could also be drawn on by South African institutions of higher education in response to any future crises similar in disruptive magnitude to the COVID-19 pandemic.