The use of xenobiotic compounds in animal husbandry has given rise to consumer anxieties regarding residual risk and food safety. Thus, animal tissues have become main samples for residue analysis and food safety for sedatives. In this study, a rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS/MS) method was established for the determination of 15 sedatives residues in mutton. After enzymolysis, sedatives residues in mutton were extracted by ammonium hydroxide-acetonitrile (10:90, v/v) and determined by RRLC-MS/MS with quantification by standard curve method. The calibration curves showed good linearity within the concentrations of 0.5-50 µg kg(-1) with the correlation coefficients (r(2)) ranged from 0.9639 to 0.9984. The limits of detection (LODs) and quantification (LOQs) were 0.25-2.5 and 0.5-5 µg kg(-1), respectively. The average recoveries of spikes samples were in the ranges of 74.1-116.8% with relative standard deviations of intra- and inter-day ranged from 2.6% to 11.2% and from 2.1% to 11.4%, respectively. This method is simple, sensitive and accurate in the determination of sedative residues.