Background: Relaxation, mindfulness, social support, and education (RMSSE) have been shown to improve emotional symptoms, coping, and fatigue in multiple sclerosis (MS). Biofeedback was trialed as a psychological intervention, designed to improve self-control, in two groups of patients with MS. Both groups received RMSSE, and one group additionally received biofeedback. Methods: Forty people with relapsing-remitting MS were recruited from three sites in Sydney, Australia. The mean disability score (Expanded Disability Status Scale; EDSS) was 2.41 ± 1.46 (95% confidence interval [CI], 1.46–3.36); the mean age in years was 45.9 ± 12.42 (95% CI, 41.92–49.87). Participants were randomly assigned to two active treatment groups (n = 20 per group). All participants received one 1-hour session per week for 3 weeks of RMSSE, while biofeedback equipment measured breathing rate and muscle tension. Members of one group used biofeedback screens to regulate physiological response. Results: Whole-group pre- and post-treatment scores demonstrated a reduction of 38% for anxiety and 39% for depression scores (P = .007 and P = .009, respectively). A post-treatment comparison failed to demonstrate any significant difference between the two active treatment groups in anxiety and depression scores. The biofeedback group showed significant pre- to post-treatment improvement or trends toward improvement in anxiety, fatigue, and stress (P = .05, .02, and .03, respectively). Comparison of pre-post treatment results between groups showed improvements for the biofeedback group in breathing rate and muscle tension (P = .06 and .09). Conclusions: For relapsing-remitting MS patients receiving biofeedback in addition to RMSSE, there was a demonstrable reduction in anxiety, fatigue, and stress. There was also a trend toward significant reduction of breathing rate and muscle tension in favor of biofeedback.