BACKGROUND: Sleep impairment and work-related stress are common issues that influence employee well-being and organizational outcomes. Impaired sleep depletes cognitive and emotional resources, increasing stress and the likelihood of counterproductive work behaviors directed toward the organization (CWB-O). This cross-sectional study, guided by the conservation of resources (COR) theory, explores the relationships between impaired sleep, work-related stress, and CWB-O, considering substance use as a dysfunctional coping strategy. METHODS: A sample of 302 Italian employees completed an online survey. Sleep impairment was assessed using the Insomnia Severity Index, work-related stress was assessed with the Perceived Stress Scale, CWB-O was assessed with the Counterproductive Work Behavior Checklist, and substance use as a coping strategy was assessed using the Brief COPE. A moderated mediation model was tested to examine the indirect effects of sleep impairment on CWB-O via work-related stress, with substance use moderating both the sleep–stress and stress–CWB-O relationships. RESULTS: The results supported the hypothesis that the relationship between sleep impairment and CWB-O is mediated by work-related stress. Sleep difficulties significantly increased work-related stress, which in turn led to higher levels of CWB-O. Substance use did not moderate the relationship between sleep and work-related stress. It did, however, significantly moderate the relationship between work-related stress and CWB-O, with higher levels of substance use amplifying the impact of stress on behavioral dysregulation. CONCLUSION: This study contributes to our understanding of how impaired sleep, work-related stress, and substance use interact to influence deviant behaviors at work. The findings align with COR theory, highlighting the role of resource depletion and dysfunctional coping in workplace behavior, and suggest that organizational interventions should also consider programs aimed at improving sleep quality and addressing substance use to reduce the likelihood of deviant behaviors at work.