Aim Health Locus of control (LOC) refers to the individual’s beliefs regarding control over their life outcomes. This study aimed to determine the influence of LOC on clinical and psychosocial aspects associated with multiple sclerosis (MS).

Methods 5059 participants with MS completed a questionnaire pack as part of the ongoing Trajectories of Outcome in Neurological Conditions (TONiC) study. Associations between predominant LOC, measured by the Multidimensional Health Locus of Control Scale, and a range of sociodemographic and clinical variables were explored.

Results Each LOC predominance was found to be significantly associated with all of the clinical variables and age, but not gender or educational level. When controlling for level of disability, Chance (CLOC) was associated with higher self-efficacy and quality of life than Powerful Others (PLOC), while Internal (ILOC) had no influence on the variables. A change in LOC away from ILOC was found with disease progression.

Conclusions In MS, believing that health is controlled mainly by chance, rather than healthcare profes- sionals or one’s self, confers the most benefit with regards to quality of life. The observed shift away from internality of LOC with MS progression may not be maladaptive, but rather a protective adaptation to reduce psychological distress.