Objectives: The objective of the present study was to test the moderating impact of an unknown pain etiology on the relationship between psychological factors and chronic pain intensity and disability. Methods: N = 471 chronic pain sufferers presented to an online Cognitive Behavioral Therapy randomized control trial, known as the Pain Course. Participants’ etiology was classified as medically unexplained or medically explained via interview and self-reported data. Standardized psychological measures at baseline were used in a non-hierarchical cluster analysis, which allocated chronic pain participants into mutually exclusive groups. Results: Four distinct clusters were identified: Psychologically healthy, mild psychological distress, high psychological distress, and average. The profile with high psychological distress experienced the greatest pain intensity (mean: 6.44 (SD = 1.66)) and disability (mean: 17.53 (SD: 3.65)). This relationship was not moderated by preceding pain etiology being medically explained or unexplained (χ2 (3) = 0.45, p = 0.93 and χ2 (3) = 7.07, p = 0.07 respectively). Conclusion: These findings indicate that an unknown pain etiology has little role in altering the relationship between psychological factors and pain disability in individuals experiencing chronic pain. This suggests that the psychological association with pain disability and intensity experienced by people with medically unexplained symptoms is similar to people with medically explained symptoms.