In patients with multiple sclerosis (MS) and healthy controls (HC) we studied circulating MAIT cells and MAIT cell subtypes expressing CXCR3 and CCR6 by flow cytometry. Absolute numbers of MAIT cells and specifically Tc17-like MAIT cells were lower in patients with primary progressive MS (PPMS) than in controls. Low numbers of Tc17-like MAIT cells were associated with smoking and high concentrations of myelin basic protein in the cerebrospinal fluid. Treatment with alemtuzumab and dimethyl fumarate decreased MAIT cell frequencies. Altogether, we have identified specific MAIT cell subtypes related to PPMS, smoking and demyelination, and MAIT cell effects of MS therapies.