Background: Multiple Sclerosis (MS) is a chronic disease for which there are multiple disease modifying therapies and symptomatic medications. Impaired self-efficacy of medication management can result in sub-optimal outcomes. Cognitive impairment in people with MS (PwMS) can impact multiple cognitive domains (CD) to varying degrees and combinations. The relationship of cognitive impairment across multiple CD to medication management in PwMS remains uncertain. Impaired medication management might adversely impact well-being, as well as social and physical functioning. Improved awareness of patient centric impaired self-efficacy of medication management might provide proactive opportunities for intervention. Objectives: To explore the relationships between self-efficacy of managing medication and cognition function in PwMS. Methods: Retrospective chart review of PwMS who underwent standardized multi-domain computerized cognitive testing (CAB, Ntrax) and completed patient reported outcomes (PRO) including Self-Efficacy for Managing Medication and Treatments (MM-4). CAB includes 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual spatial (Vis), verbal function (Ver), motor skills (Mot) as well as a global cognitive summary score (GCS). Results: 338 PwMS (74% female, age = 50.6 ± 11.7 years) Regression modeling showed the following relationships between MM-4: GCS (r2 = 0.16, p = p < 0.05), Mem (r2 = 0.01, p < 0.05), Exe (r2 = 0.32, p < 0.05), Vis (r2 = 0.05 p < 0.05), Ver (r2 = 0.07, p < 0.05), Att (r2 = 0.29, p < 0.05), Inf (r2 = 0.21, p < 0.05), Mot (r2 = 0.08 p < 0.05). Conclusions: Increasing cognitive impairment is associated with worse self-efficacy for managing medication and treatment. Progressive impairment of Specific CD are associated with progressive impairment of MM-4. Executive function shows the most significant relationship with MM-4 followed by attention and information processing. Incorporation of CAB into routine care can provide value added patient centric information that might offer opportunities to enhance care and outcomes in PwMS.