Background: Historically, there has been limited research on care partners of patients with multiple sclerosis (MS). Employers, health care providers, and care partners will benefit from an improved understanding of the impact of MS on care partners. Objectives: To evaluate the 1-year clinical and economic impact on employee care partners of patients with MS by disease severity. Methods: Employees with spouses/partners/dependents with MS were selected from the WorkPartners database (1/1/201012/31/2019). Eligibility criteria were: a spouse/partner/dependent with ?3 MS-related (ICD-9-CM/ICD-10-CM: 340.xx/G35) inpatient, outpatient, or MS disease-modifying therapy (DMT) claims within 1-year (latest claim=index date); continuous enrollment 6?months pre-/1-year post-index; and age 1864. Employee care partners demographic and clinical characteristics, and direct and indirect costs were compared across the MS severity categories. Costs were calculated using two-stage (logistic-generalized linear model) regression. Results: Among 1041 eligible employee care partners, 358(34.4%) had spouses/partners/dependents with mild MS, 491(47.2%) moderate, and 192(18.4%) severe. Mean (standard error [SE]) care partner age was younger for mild vs. moderate/severe patients (mild 49.0[0.5], moderate 50.5[0.4]; severe 51.7[0.6]). The percentage of female care partners (SE) was: mild 24.6%(2.3%); moderate 19.8%(1.8%), severe 27.6%(3.2%; severe vs. moderate p=0.026). Mean (SE) baseline Charlson Comorbidity Index scores for care partners were: mild 0.28(0.05); moderate 0.30(0.04); severe 0.27(0.06). A greater proportion of care partners of moderate/severe vs. mild patients had hyperlipidemia (32.6%/31.8% vs 21.2%), hypertension (29.5%/29.7% vs 19.3%), gastrointestinal disease (20.8%/22.9% vs 13.1%), depression (9.2%/10.9% vs 3.9%), and anxiety (10.6%/8.9% vs 4.2%). Care partner adjusted mean (SE) direct medical costs were greater for partners of moderate vs. mild/severe patients (mild $5025[$390], moderate $7887[$518], severe $5302[$561]; both p<0.001). Non-DMT pharmacy costs (SE) were lower for partners of mild vs. severe/moderate patients (mild $1442[$126], moderate $1984[$145], severe $2363[$278]; both p<0.005). Sick leave costs (SE) were greater for partners of mild/severe vs. moderate patients (mild $485[$76], moderate $286[$45], severe $611[$130]; both p<0.05). Conclusions: Employees with spouses/partners/dependents with MS had comorbidities and direct and indirect costs that varied with MS severity.