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Purpose: Sexual dysfunction and low sexual satisfaction are common among individuals with multiple sclerosis (MS); however, little is known about factors that influence sexual satisfaction within this population. As such, the purpose of this study was to investigate the extent to which changes in negative and positive partner support predict sexual satisfaction levels over time in individuals with MS. Design: Eighty-one individuals with MS completed measures of sexual dysfunction, sexual satisfaction, partner social support, and depression. Data from baseline and posttreatment follow-up were obtained from a larger randomized clinical trial of telephone-administered psychotherapy for depression in a population with MS. Multiple regression analyses were conducted with change in overall sexual satisfaction from baseline to posttreatment as the outcome variable. Results: After controlling for age, gender, sexual dysfunction, years diagnosed with MS, and depression severity, those with increased positive partner support reported significant improvement in sexual satisfaction over time (β = .50, p < .001), as did individuals with decreased negative partner support (β = .36, p < .01). Conclusions: Results provide evidence that both positive and negative partner support have a distinctive role in the outcome of sexual satisfaction for individuals with MS. Understanding the unique role of positive and negative forms of partner support on sexual satisfaction will help lead to future interventions to improve sexual satisfaction among couples.