Using ammonium dodecyl sulfate (ADS) as the surfactant, the response of three common interfaces in the direct coupling of microchip micellar electrokinetic chromatography with electrospray ionization mass spectrometry was studied. In the range of 1040?mM surfactant, a conventional sheath liquid interface provided poorer sensitivity than both sheathless interface and low-sheath-flow interface. At a surfactant concentration <20?mM, a low-sheath-flow interface exhibited less sensitivity than a sheathless interface; however, it outperformed the sheathless interface above a concentration of 20?mM. At a surfactant concentration above 20?mM, signal reduction due to dilution of the analyte compensated by signal enhancement gained from a reduction in ion suppression effect. The difference in responses of the interfaces was mainly due to the dilution effect, whereas the effect of flow rate became an important factor when the difference in responses between the interfaces was not significant. The utility of the PMMA microchip MEKC/MS using a low-sheath-flow interface was demonstrated by the analysis of sulfonamides at a concentration of 40?mM. The interday precision was in the range of 4.914.5%, and the LOD was in the range of 0.341.03?ng/mL (MEKC/MS/MS).