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This study analyzed the effects of work interruptions as a stressor and appreciation of employees by supervisors as a resource with regard to four parameters of well-being, postulating main effects and interactions. Using latent moderated structural equation modeling, we analyzed longitudinal data on 208 employees at seven different companies who completed an online questionnaire twice. There were no main effects; however, the interactions between work interruptions and appreciation by supervisors were significant, and in the expected direction. Appreciation by supervisors moderated the effects of interruptions on the four parameters of employees’ well-being: job satisfaction, self-efficacy, job-related depressive mood, and sleep problems. These results held after accounting for conceptually relevant control variables, namely, time pressure, job control, and social support by supervisors. There were no …