A key diagnostic criterion of Somatic Symptom and related Disorders (SSD) comprises significant distress and excessive time-and-energy consuming thoughts, feelings, and behavior pertaining to somatic symptoms. This diagnostic criterion is lacking in central sensitivity syndromes (CSS), such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome. This strong emphasis on disturbed psychological processing of somatic symptoms, suggests that psychological flexibility is low in SDD. Psychological flexibility is defined as the ability to approach difficult or challenging internal states (thoughts, emotions, and bodily sensations) in a non-judgmental, mindful way, and being committed to pursue one's values. To clarify the potential significance of psychological flexibility in SSD, we examined its levels in 154 people referred to specialized treatment for SDD, as compared to reference groups from the general population encompassing 597 people with CSS and 1422 people without SSD or CSS (controls). Mean levels of psychological flexibility (adjusted for demographic covariates) were lowest for SSD and highest for controls (F = 154.5, p < 0.001, pη2 = 0.13). Percentages of people with low psychological flexibility (<0.8 SD below the mean of controls) were: SSD 74%, CSS 42%, controls 21%. In SSD, higher psychological flexibility was associated with better mental health (β = 0.56, p < 0.001), but interaction analysis rejected that psychological flexibility preserved health when having more severe somatic symptoms (β ≤ 0.08, p ≥ 0.10). The results indicate that lower psychological flexibility is a prevalent problem in SSD that is associated with lower mental health. This suggests that it is worthwhile to take account of psychological flexibility in SSD in screening, monitoring, and therapy.