Purpose: The aim of this study was to test the Common Sense Model of Self-Regulation among persons with multiple sclerosis (MS), hypothesizing direct relations between illness beliefs and psychological adjustment, and indirect relations through coping strategies and social support.Materials and methods: Questionnaires were administered cross-sectionally to 680 participants (Mage =40.1; 64.4% women) recruited in eight MS units to assess illness beliefs, coping strategies, social support, and adjustment indicators including life satisfaction, psychological well-being, mental health, and depression. Multiple mediational analyses were conducted to identify direct and indirect paths connecting illness beliefs to psychological outcomes.Results: Controlling for disability level, significant direct and indirect relationships were observed: Beliefs on illness coherence, personal and treatment control were associated with better adjustment; emotion representations and cyclic timeline with worse adjustment; illness identity, consequences, psychological and chance/bad luck causes with mixed positive and negative outcomes. Notably, findings identified recurrent and unique pathways connecting illness beliefs to the different indicators through meaning- and problem-focused coping strategies, avoidance and social support.Conclusions: The Common Sense Model can represent a useful framework to be tested in rehabilitation programs, jointly addressing illness beliefs and coping resources for the promotion of psychological adjustment among persons with MS.IMPLICATIONS FOR REHABILITATIONBased on the Common Sense Model, the beliefs held by persons with MS about their illness are related to various aspects of psychological adjustment in multiple ways, both directly and indirectly through engagement in specific coping strategies and perception of social support.Clinicians supporting patients’ adjustment may take into account that some illness beliefs were consistently associated with positive adjustment, some with poor adjustment, and some yielded mixed positive and negative results.Some ways in which coping strategies and social support connected illness beliefs to psychological adjustment were specific to the adjustment indicator under consideration including satisfaction with life, psychological well-being, mental health and depression.It may be worth testing comprehensive psychological interventions with the aim of raising awareness of one’s illness beliefs, the strategies enacted in response to these beliefs, and the positive and negative relations of these processes with psychological adjustment, encompassing broad areas of individuals’ lives and not only health-related issues or depression.