Background: Social stigma is a common experience among persons with multiple sclerosis (PwMS), and it may impact daily functioning, quality of life, and depression. However, research into the drivers and correlates of stigma in PwMS has been limited. Objectives: To characterize the relationships between demographic/clinical attributes and quality of life (QoL) measures with stigma in PwMS. Methods: We conducted a cross-sectional study of participants in iConquerMS, a participant-powered MS research network. Participants complete baseline and biannual surveys that capture demographic/clinical attributes and QoL (i.e., Quality of Life in Neurological Disorders [Neuro-QoL] surveys), and other outcomes. There were 2,054 PwMS who completed the Neuro-QoL and demographic surveys within 90 days. The Neuro-QoL Stigma 8-item Short Form was categorized into terciles (low stigma: ?10; moderate: 11-16; high: ?17) and was the dependent variable for two multivariable ordered logistic regression models: 1) demographic/clinical attributes, and 2) demographic/clinical attributes + Neuro-QoL measures: ability to participate in social roles, satisfaction with social roles, communication, cognition, depression, fatigue, lower limb functioning, upper limb functioning, and sleep disturbances. Results: The study population was 78% female, 92% White, 62% relapsing remitting (RR), 20% secondary progressive (SP), 12% primary progressive (PP), and had a mean age of 51 years. In model 1, PwMS who were younger; had a shorter disease duration; SP/PPMS; less than a college education; were on disability, a homemaker, or unemployed; and divorcees had significantly higher experiences of stigma (p<0.05). The strongest associations were for SP vs RR (odds ratio [OR]=2.3, p<5×10-8), and being on disability (OR=3.4, p<5×10-8), a homemaker (OR=2.1, p<0.005), or unemployed (OR=2.5, p<5×10-5) compared to those employed. In model 2, PwMS who were less able (p<0.05) or less satisfied (p<5×10-8) with their social roles, had more severe depression symptoms (p<5×10-5), leg impairment (p<5×10-7), and sleep disturbances (p<5×10-8), had significantly higher experiences of stigma. Once accounting for the QoL measures, a shorter disease duration was independently associated with higher stigma. Conclusions: Understanding factors that contribute to higher levels of stigma are an important first step for patients and their care team members. Addressing co-occurring depression and sleep disturbances may be opportunity to reduce stigma for PwMS.