To evaluate the association between social capital (SC) and the physical and psychological impact of multiple sclerosis (MS).A cross-sectional study was conducted among people with MS (pwMS) at The Royal London Hospital, London, UK. Participants completed a survey including the Multiple Sclerosis Impact Scale-29 (MSIS-29), the Hospital Anxiety and Depression Scale (HADS), the self-reported EDSS and a SC questionnaire (SCQ). The SCQ assessed personal relationships, social support networks, civic engagement, and trust and cooperative norms. Kendall's tau correlation test was performed to measure the correlation between SC and MSIS-29 scores, and multiple linear regressions were conducted to find the best outcome prediction model.236 pwMS participated in the study. Median age was 43.5 years (IQR 35-52). Of the total, 168 (71.2%) were female and 180 (76.3%) had relapsing-remitting MS. Median MSIS-29 scores were 23.7 (IQR 8.8-57.5) for the physical scale and 38.9 (IQR 16.7-55.6) for the psychological scales. Total SC scores were significantly correlated with the MSIS-29 physical (τb = -0.09, P = .02) and psychological scores (τb = -0.23, P < .001). After adjusting for possible confounders, the "personal relationships" domain had a significant effect on the MSIS-29 physical scores (β = -2.70, SE = 1.34; P = .045). Total SC (β = -1.08, SE = 0.33; P = .001) and the "personal relationships" (β = -2.60, SE = 1.20; P = .031) and "trust and cooperative norms" (β = -1.40, SE = 0.61; P = .024) domains had a significant effect on the MSIS-29 psychological scores.Higher levels of SC were associated with lower physical and psychological impact of MS. Emerging evidence on SC and its effects on MS should be translated into interventions designed to promote the health and well-being of pwMS.