Background: B-cell depleting agents are FDA approved for the treatment of RRMS (ocrelizumab (OCR) and ofatumumab (OFA)) and PPMS (ocrelizumab). In the case of OCR, prior studies have raised concerns about patients ability to form antibodies in response to various antigens, especially SARS-CoV-2. Several studies have reported attenuated antibodies against SARS-CoV-2 following a course of COVID-19 infection. In addition, emerging data have shown an attenuated humoral response to vaccines against SARS-CoV-2. Objectives: The objective of this study is to determine whether OCR and OFA attenuates the antibody response to various SARS-CoV-2 vaccines in patients with MS as compared with other disease modifying therapies (DMTs). Methods: This is a case-control study looking at the odds of developing antibodies to three SARS-CoV-2 vaccines (Pfizer-BioNTech, Moderna, and Johnson & Johnson) in patients treated with OCR or OFA versus other disease modifying therapies. Patients who did not have a prior COVID-19 infection and received one of the three vaccines were tested for antibodies against the SARS-CoV-2 spike protein (Labcorp, semi-quantitative total antibody) at least two weeks following the final dose of the vaccine. Groups (B-cell, sphingosine 1-phosphate (s1p) modulators, other medication, and no medication) were compared on antibody level. Dichotomous antibody response was tested using logistic regression models, and the quantitative response was tested using ANCOVA adjusted for covariates (age, sex, race, MS type, disease duration, vaccine, and lymphocyte count). P-values <0.05 were considered significant. Results: Sixty-seven patients were enrolled in the study, with 17 on OCR, 3 on OFA, 12 on s1p modulators, 29 on other DMT, and 6 not currently on any DMT. Patients who received OCR or OFA had decreased odds of forming antibodies (OR 0.031, p<0.001, 95% CI (0.003-0.268)). Patients who received s1p modulators did not have decreased odds of forming antibodies (OR 0.413, p=0.413, 95% CI (0.28-21.7). Conclusions: Patients who received B-cell depleters within the prior 6 months of SARS-CoV-2 vaccination had decreased odds of developing antibodies compared with other DMTs. In line with other similar research, this suggests that OCR attenuates the antibody response to SARS-CoV-2 vaccines. Although levels of antibodies were decreased with s1p modulators, the odds of forming antibodies were not influence by s1p modulators.