Background <p>Counterproductive work behaviour (CWB), a deviant intentional behaviour by employees poses a negative detrimental effect in healthcare institutions, exacerbating reduced quality care, and organizational financial and human capital loss. This study examined the association of perception organizational politics and job stress on counterproductive work behaviour among nurses in Enugu, South-east, Nigeria.</p> Method <p>228 nurses (209 females, 19 males) were purposively sampled from two public tertiary health facilities in Enugu, Nigeria through multistage sampling (purposive, quota and simple random). The study adopted a quantitative approach using cross-sectional design and hierarchical multiple regression statistics was used to analyze the data. Data was collected using the Perceived Organizational Politics Scale; Perceived Job Stress Scale; and Workplace Deviance Scale.</p> Results <p>Organizational politics (<i>r</i> = .33, <i>p</i> &lt; .01) and Job stress (<i>r</i> = .30, <i>p</i> &lt; .01) significantly and positively related to Counterproductive Work Behaviour, resulting that high stress and perceived politics experienced by nurses makes them engage in deviant behaviors which can harm the organization either intentionally or unintentionally. Perceived organizational politics is positively associated with CWB (β = 0.34, <i>p</i> &lt; .000), while perceived job stress was found not to be associated with Counterproductive Work Behaviour (β = − 0.48, <i>p</i> &gt; .098). Nurses increase perception of organizational politics is a key driver of likelihood engaging in CWB than when experiencing stress at work.</p> Conclusion <p>Efforts should be targeted at reducing politics and unfair treatment of employees and promote a healthy work environment in health facilities, rooted in transparency, fairness, open communication and ethical leadership which improves nurses’ commitment, productivity and efficient service delivery and reduces nurses’ migration.</p> Clinical trial number <p>Not applicable.</p>