Few studies have explored mediators between medication-related support and medication adherence for individuals with rare, systemic autoimmune conditions. Using the Information-Motivation-Behavioral Skills model, we tested whether depressive symptomatology and medication adherence self-efficacy mediated the relationship between adherence support and changes in medication adherence among vasculitis patients, and whether support from physicians and partners differentially affected medication adherence. Vasculitis patients (n = 172) completed baseline and follow-up questionnaires about their medication adherence and perceived adherence support. Bootstrapped mediation analyses tested the effects of physician and partner support on changes in medication adherence. Adherence self-efficacy mediated the relationship between physician support and changes in medication adherence (B = 0.05, SE = 0.03, 95% CI 0.01, 0.13). Neither self-efficacy nor depressive symptomatology mediated the effects of partner support. Although physicians spend little time with patients, they can increase patients' confidence about taking medications correctly and potentially improve health outcomes by bolstering medication adherence.