This study examined the influence of negative major life events (MLEs) on work engagement and affective commitment, considering the personal resources of emotion regulation and mindfulness. Affected employees ( N = 182) were surveyed at three measurement points to analyze relationships between MLE-related strain, work engagement, and affective commitment, as well as potential moderating effects. Regression analyses revealed positive direct effects of emotion regulation on both outcomes and a positive direct effect of mindfulness on work engagement, whereas no direct associations between MLE-related strain and the outcomes were observed. Contrary to the hypothesized assumptions, moderation analyses indicated reinforcing effects of emotion regulation and mindfulness on affective commitment and a reinforcing moderation effect of emotion regulation on work engagement. Given the high prevalence of COVID-19-related MLEs, the study provides additional insights into the role of personal resources in coping with profound changes in the work context.