Aim Identifying motivational factors that facilitate physical activity engagement in adults with multiple sclerosis (MS) is important given beneficial health outcomes. The purpose of this study was to examine the relationship between physical activity of adults with MS and perceived spousal behaviors underlying self-determination. Methods One-hundred and twelve individuals with MS completed the Patient Determined Disease Steps, Physical Exercise Self-Efficacy Scale, Spousal Support for Physical Activity Scale, and Godin Leisure-Time Exercise Questionnaire. Descriptive statistics, scale reliabilities, and bivariate correlations were obtained. To examine the influence of perceived spousal behavior on total metabolic equivalents, a regression analysis was conducted. Results All subscales were found to be highly reliable. Strong and significant associations between each of the variables and physical activity existed except for that of expectations, social control, and self-efficacy. Physical activity was best predicted by spousal behaviors supporting the self-determination constructs ofrelatedness,competence, andautonomy(R = 0.49,R-2=0.24,F-8,F-93=2.27,p < 0.05), with spousal support contributing 14.8% to total self-determined physical activity. Conclusions Given the significant role of the spouse in fostering intrinsic motivation for physical activity in adults with MS, delivering more partner-oriented and targeted interventions that build relationship, competence and autonomy appear warranted.