As narcotic analgesics, fentanyl compounds have been commonly produced and widely used during surgical procedures. The residual and waste of fentanyl compounds have potential harmful impacts on the environment and human health. The oxidative degradation of fentanyl compounds by sodium bromate mixed systems was studied. Factors influencing the oxidation reaction, including molar ratio of NaBrO3/H+/SO32−, molar ratio of NaBrO3/fentanyl and pH, were investigated. Fentanyl, carfentanil and 3-methylfentanyl were able to be completely degraded in 30 minutes by a NaBrO3 mixed system under optimum conditions, the molar ratio of NaBrO3/H+/SO32− equal to 20:3:10, the molar ratio of NaBrO3:fentanyl compounds 50:1 and pH = 4. Sufentanil was only able to be degraded by 74% under the same conditions. The degradation products of the fentanyl compounds detected and identified by gas chromatography/mass spectrometry suggested several possible degradation pathways.