Case studies suggest hypnosis with a virtual reality (VR) component may be an effective intervention; although few follow-up randomized, controlled trials have been performed comparing such interventions with standard hypnotic treatments. Thirty-five healthy participants were randomized to self-hypnosis with VR imagery, standard self-hypnosis, or relaxation interventions. Changes in sleep, cortisol levels, and mood were examined. Self-hypnosis involved 10- to 20-min. sessions visualizing a healthy immune scenario. Trait absorption was also recorded as a possible moderator. Moderated regression indicated that both hypnosis interventions produced significantly lower tiredness ratings than relaxation when trait absorption was high. When trait absorption was low, VR resulted in significantly higher engagement ratings, although this did not translate to demonstrable improvement in outcome. Results suggest that VR imagery may increase engagement relative to traditional methods, but further investigation into its potential to enhance therapeutic efficacy is required.