ABSTRACT The aim of this intensive longitudinal study was (1) to explore the temporal evolution of two mental health indicators (anxiety and depressive symptoms, and insomnia) throughout COVID-19 lockdown in Spain, and (2) to examine its association with two work-related stressors (job insecurity and work-family conflict). A sample of 1519 participants responded to several questionnaires during the lockdown (between 16 March and 29 April 2020). Results of latent growth modelling showed a curvilinear increase of our two mental health indicators over time (a logarithmic growth for anxiety and depression, accentuated during the first part of the lockdown, and a quadratic growth for insomnia, accentuated during the second part). Regarding its association with work-related stressors, we found that higher levels of job insecurity and work-family conflict were related to higher levels of anxiety, depression, and insomnia. Additionally, we found a significant interaction between time and the two forms of work-family conflict (work-to-home and home-to-work), showing that people with more work-family conflict experienced stronger growth in all mental-health indicators. Overall, this study contributes to the description of the temporal dynamics of mental health during the COVID-19 outbreak in Spain, as well as its association with two key work-related stressors.