Low desire in women is the most common sexual difficulty, and stress has been identified as a significant predictor of symptoms. We evaluated a mindfulness-based cognitive therapy (MBCT) group treatment versus a sex education comparison group treatment (STEP) on self-reported stress and on the physiological stress response measured via morning-to-evening cortisol slope in 148 women with a diagnosis of sexual interest/arousal disorder (SIAD). Perceived stress decreased following treatment in both groups, and significantly more after MBCT. The cortisol slope was steeper (indicative of better stress system regulation) from pre-treatment to 6-month follow-up, with no differences between the groups. As an exploratory analysis, we found that the reduction in perceived stress predicted increases in sexual desire and decreases in sex-related distress for participants after MBCT only. These findings suggest that group mindfulness targeting women with low sexual desire leads to improvements in self-reported and physiological stress, with improvements in self-reported stress partially accounting for improvements in sexual desire and distress.