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The present study examined the moderating influences of chronic prevention focus and affective organizational commitment on the relationship between perceived job insecurity and emotional exhaustion through a survey on a sample of 312 employees of a private health institution on the west coast of Turkey. We hypothesized that chronic prevention focus would strengthen, whereas affective organizational commitment would weaken the positive association between job insecurity and emotional exhaustion. We further predicted that affective organizational commitment would exert its buffering effect primarily among employees with a high chronic prevention focus, thus reducing the harmful effect of chronic prevention focus. We found that job insecurity was positively associated with emotional exhaustion only among employees with a high chronic prevention focus. There was no moderation effect by affective organizational commitment in the association between job insecurity and emotional exhaustion. On the other hand, a significant 3-way interaction effect showed that affective organizational commitment had differential influences on the job insecurity and emotional exhaustion link depending on chronic prevention focus. Consistent with our expectations, among employees with high chronic prevention focus, affective organizational commitment eliminated the positive association between job insecurity and emotional exhaustion. However, unexpectedly affective organizational commitment strengthened the positive association between job insecurity and emotional exhaustion among employees with low chronic prevention focus. The implications of the present findings are discussed.