As a response to the COVID-19 pandemic, many governments encouraged or mandated homeworking wherever possible. This study examines the impact of this public health initiative on homeworkers’ well-being. It explores if the general factors such as job autonomy, demands, social support and work–nonwork conflict, which under normal circumstances are crucial for employees’ well-being, are outweighed by factors specific to homeworking and the pandemic as predictors of well-being. Using data from four-week diary studies conducted at two time periods in 2020 involving university employees in the UK, we assessed five factors that may be associated with their well-being: job characteristics, the work–home interface, home location, the enforced nature of the homeworking, and the pandemic context. Multi-level analysis confirms the relationship between four of the five factors and variability in within-person well-being, the exception being variables connected to the enforced homeworking. The results are very similar in both waves. A smaller set of variables explained between-person variability: psychological detachment, loneliness and job insecurity in both periods. Well-being was lower in the second than the first wave, as loneliness increased and the ability to detach from work declined. The findings highlight downsides of homeworking, will be relevant for employees’ and employers’ decisions about working arrangements post-pandemic, and contribute to the debate about the limits of employee well-being models centred on job characteristics.