Worry is a cognitive activity in which potential problems are anticipated and enumerated in an attempt to control the future. Worry has been associated with dysregulation of the autonomic nervous system, which may extend to the immune system. The relationship between trait worry and immune parameters was investigated at three follow-up points after the Northridge earthquake in a sample of 47 hospital employees. Participants with scores above the median on a trait worry measure had fewer natural killer cells than participants with worry scores below the median and controls. This effect was not mediated by intrusive thoughts, avoidance, anxious mood, or health behavior. These results suggest that worry may have a detrimental effect on the regulation of natural killer cells during stress. This effect may be due to differences in autonomic responsiveness associated with worry.