RAMP3 is a chaperone protein that aids in the transport, activity modulation and pharmacological switch of many G-protein coupled receptors (GPCRs), such as chemokine receptors. GPCRs are involved in immune cell recruitment and activation, but the role of RAMP3 in the immune system has not been explored. We found that Ramp3 transcripts were highly expressed in innate-like T cells in the lungs of mice, particularly mucosal-associated invariant T (MAIT) cells. Ramp3-/- mice had an increased number of lung MAIT cells. These differences were even higher after vaccination with a live attenuated Salmonella vaccine strain that expresses MAIT-cell antigens. Both at steady-state and after vaccination, MAIT cells from Ramp3-/- mice had increased surface CXCR6, a chemokine receptor that has been associated with lung homing and memory T cell maintenance in the periphery. These data suggest RAMP3 decreased surface expression of CXCR6. Consequently, Cxcr6-/- mice had drastically lower MAIT cells numbers after Salmonella vaccination, although these cells had comparable levels of the activation marker CD69 compared to wild-type mice, suggesting the MAIT cells were functional. Interestingly, increased lung MAIT cells was accompanied with increased inflammation and neutrophil infiltration in the Ramp3-/- mice after infection, as well as increased bacterial burden for multiple models of lung infections, suggesting an immune-pathological effect is occurring in these mice. Altogether, Ramp3 has an unexpected role in innate immunity and innate-like T cells, in part, through regulating expression of CXCR6 or other GPCRs.