Emotion processing has been demonstrated to have a strong impact on somatic symptom perception. In the current quasi-experimental trial associations between the application of emotion regulation strategies and symptom-related outcomes were examined in subjects with medically unexplained physical symptoms (MUS; n = 48) and in mentally healthy individuals (n = 48). Somatic symptoms were repeatedly induced four times in both samples. After each symptom induction, participants were instructed to apply another of four emotion regulation strategies. Symptom-related outcomes were rated before and after a strategy was applied. Hierarchical linear models showed that in the MUS group cognitive reappraisal was significantly and acceptance was marginally associated with lower symptom annoyance scores compared with compassionate self-support. In healthy subjects distraction was associated with better mood scores compared with compassionate self-support. Future research should examine the effects of acceptance and cognitive reappraisal strategies applied by MUS subjects over a longer period of time.