A sensitive, simple and rapid method using LC/MS and LC/MS/MS assay for selective serotonin reuptake inhibitors (SSRIs), in human serum or plasma was investigated in this study. In this method, three SSRIs, paroxetine, sertraline and fluvoxamine were measured; dextromethorphan was used as internal standard (IS). Serum or plasma samples with or without the compounds and IS, which were mixed with formic acid, were directly subjected to LC/MS. In MS spectra, [M + 1]- ions for paroxetine and fluvoxamine, [M - 31]- ion for sertraline were observed as base peaks. For MS/MS analyses, [M + 1] -ions of the compounds were used as precursor ions for these identification and quantitation. The three compounds could be identified above 100 ng/ml serum, using MS and dependent MS/MS. For three compounds, the calibration curves were linear in the range 5 - 80 ng/ml in the serum and the detection limits were under 5 ng/ml serum and 10 ng/ml plasma, respectively. These results indicate that this presented method can be useful to determine the SSRI in human serum or plasma.