Health anxiety is characterized by the misinterpretation of body sensations as signs of an illness, leading to health-related worry and increased healthcare utilization. Research has demonstrated the effectiveness of mindfulness-based interventions in the treatment of severe health anxiety, yet mechanisms of this association remain unexplored. Therefore, the present investigation sought to examine the indirect effect of mindfulness on health anxiety through intolerance of uncertainty (IU) or fear of the unknown. Undergraduate psychology students completed a series of online self-report measures for course credit. Bias-corrected bootstrapping (k = 10,000 samples) was used to generate a 95 % confidence interval to test the significance of the indirect effect. There was a significant indirect effect of greater levels of mindfulness on lower levels of health anxiety through decreases in intolerance of uncertainty. Higher levels of mindfulness may lead internal experiences to be perceived as less threatening, thereby increasing one’s ability to tolerate uncertainty and decreasing the need to worry and engage in safety behaviors that maintain health anxiety.