It is well established that bacteria are capable of degrading selected drugs during decomposition. The aim of this study was to investigate the stability of several serotonin-selective reuptake inhibitor antidepressants and venlafaxine during putrefaction in porcine liver macerate inoculated with porcine cecal contents rich in bacteria. Blank liver matrices, sterile liver macerates, and sterile aqueous controls were included with the experiment performed for 57 days at 20°C under anaerobic conditions. A liquid chromatography/mass spectrometry method was developed for quantitative determination of the drugs investigated in both sterile and decomposed liver matrices. The method was found to encounter matrix effects not detected during the validation stage. Citalopram, paroxetine, sertraline, venlafaxine, and fluoxetine were found to be stable under the experimental conditions; however, fluvoxamine was found to be decreased by c. 50% over 57 days in bacterially inoculated liver macerate. This study suggests that fluvoxamine concentrations in cases with evidence of decomposition/putrefaction should be interpreted with extra caution.