Exposure-based cognitive behavior therapy (CBT) has been shown to be effective in the treatment of severe health anxiety, but little is known about mediators of treatment effect. The aim of the present study was to investigate mindful non-reactivity as a putative mediator of health anxiety outcome using data from a large scale randomized controlled trial. We assessed mindful non-reactivity using the Five Facets Mindfulness Questionnaire-Non-Reactivity scale (FFMQ-NR) and health anxiety with the Short Health Anxiety Inventory (SHAI). Participants with severe health anxiety (N = 158) were randomized to internet-delivered exposure based CBT or behavioral stress management (BSM) and throughout the treatment, both the mediator and outcome were measured weekly. As previously reported, exposure-based CBT was more effective than BSM in reducing health anxiety. In the present study, latent process growth modeling showed that treatment condition had a significant effect on the FFMQ-NR growth trajectory (alpha-path), estimate = 0.18, 95% CI [0.04, 0.32], p = .015, indicating a larger increase in mindful non-reactivity among participants receiving exposure-based CBT compared to the BSM group. The FFMQ-NR growth trajectory was significantly correlated with the SHAI trajectory (13 -path estimate = -1.82, 95% CI [-2.15, -1.48], p amp;lt;.001. Test of the indirect effect, i.e. the estimated mediation effect (an) revealed a significant cross product of 0.32, which was statistically significant different from zero based on the asymmetric confidence interval method, 95% CI [0.59, -0.06]. We conclude that increasing mindful non-reactivity may be of importance for achieving successful treatment outcomes in exposure-based CBT for severe health anxiety.