Background: Musculoskeletal and mental disorders are often comorbid, with complex correlations of pain, impairment due to pain, disability, and psychological wellbeing. This study investigates the role of psychological wellbeing in a worksite healthcare program for employees within a German randomized controlled trial. Methods: For our analyses we used data of the module for minor musculoskeletal complaints (N = 180). The intervention included a workplace-related training and case manager support. Results: Changes over time were significant in the disability score (t(179) = 9.04, p < 0.001), pain intensity (t(179) = 9.92, p < 0.001), and psychological wellbeing (t(179) = −4.65, p < 0.001). Individuals with low vs. high psychological wellbeing showed significant differences in their disability scoret0,t1 (tt0(178) = −4.230, pt0 < 0.001, tt1(178) = −2.733, pt1 < 0.001), pain intensityt0,t1 (tt0(178) = −3.127, pt0 < 0.01, tt1(178) = −3.345, pt1 < 0.01, and motivationt0 (tt0(178) = 4.223, pt0 < 0.001). The disability score∆ mediates the impact of pain intensity∆ on psychological wellbeingt1 (beta = 0.155, p < 0.05). Psychological wellbeing∆ had an impact on the disability scoret1 (beta = −0.161, p < 0.01). Conclusions: The lower the psychological wellbeing is at an intervention’s beginning, the higher the potential is for its improvement, which might affect individuals’ experienced impairment due to pain. In order to achieve the best outcomes, interventions should include both pain-related and psychological aspects. Future research needs to explore the causality of the found interrelationships further.