While MAIT cells are innate-like T cells specifically responding to microbial vitamin metabolites presented by MR1 molecules, it was recently shown that IL-18 produced during viral infections can contribute to MAIT cell activation. Hantaviruses cause two severe human diseases; hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia and hantavirus pulmonary syndrome (HPS) in the Americas, with case-fatality rates of up to 10% and 40%, respectively. Hantavirus infection of humans is characterized by increased vascular leakage and strong inflammatory responses displayed by high levels of pro-inflammatory cytokines and vigorous NK cell, B cell, and CD8 T cell responses. The human immune response upon hantavirus infection is believed to be an important factor in the disease pathogenesis, yet the mechanistic background to what is driving the inflammatory responses is largely undescribed. We and others recently observed that systemic IL‑18 levels are increased in HFRS and HPS patients. Here, we performed a phenotypic characterization of peripheral MAIT cells in 25 Swedish HFRS patients, during acute and convalescent phase. The frequency of MR1 tetramer-defined MAIT cells was reduced during acute HFRS, as compared to uninfected controls. The residual MAIT cells still present were characterized by an activated phenotype with increased expression of CD69, CD38, and granzyme B. In addition, MAIT cells of HFRS patients showed high expression of Ki67. These data suggest that hantavirus infection induces activation and proliferation of peripheral MAIT cells. Reduced expression of the gut homing receptors α4β7 and CCR6 further suggested that MAIT cells might have been sequestered away from circulation to mucosal sites. Continued studies will aim at investigating possible effects of hantavirus on the MAIT cell phenotype and function in vitro, and at exploring the potential role for MAIT cells in hantavirus immunopathogenesis.