Objectives: To investigate the longitudinal relationships between social support and subsequent mental health outcomes in individuals with multiple sclerosis (MS), and to examine resilience as a mediator between social support and subsequent mental health outcomes in this population.

Design: Observational, longitudinal cohort study. Participants were assessed at 4 time points over 12 months in the context of a previously reported randomized controlled trial.

Setting: Telephone-based measures administered to community-based participants.

Participants: Individuals (N=163) with MS and 1 or more of the following symptoms: depression, fatigue, and pain.

Interventions: Not applicable.

Main outcome measures: Mental health outcomes included (1) depressive symptomatology, assessed using the Patient Health Questionnaire-9; (2) anxious symptomatology, assessed using the short form of the Emotional Distress-Anxiety Scale from the Patient-Reported Outcomes Measurement Information System; and (3) general mental health status, assessed using the Mental Component Summary score from the Short Form-8 Health Survey. Resilience was assessed using the Connor-Davidson Resilience Scale.

Results: At any given time, social support from significant others, family members, and friends was significantly associated with subsequent mental health outcomes for all 3 measures assessed (all P values <.05). Resilience measured concomitantly with social support significantly mediated the relationships between social support and subsequent mental health outcomes. After controlling for resilience, most of the direct relationships between social support and mental health outcomes were no longer significant.

Conclusions: There are significant longitudinal relationships between social support, resilience, and mental health outcomes for people with MS. Given the mediating role of resilience in supporting better mental health outcomes, future clinical research and practice may benefit from an emphasis on resilience-focused psychological interventions.