OBJECTIVE： To develop a method for rapid， accurate and simultaneous determination of dexzopiclone， zolpidam and zaleplon in human plasma. METHODS： After the plasma sample was processed by liquid-liquid extraction， UPLC-MS/MS was established to detect plasma sample with carbamazepine as internal standard. The separation was performed on a Waters ACQUITY UPLC HSS T3 column with mobile phase composed of 0.1％ ammonium solution-acetonitrile （gradient elution） at flow rate of 0.2 ml/min. The column temperature was set at 40 ℃， and sample size was 5 μl. The detection was performed by multiple reaction monitoring （MRM） via electrospray ionization （ESI） source in positive mode. The mass transition ion-pairs were as follows： m/z 308.2→263.1（zolpidem）， m/z 389.3→245.0（dexzopiclone）， m/z 306.2→236.1（zaleplon）， m/z 237.3→151.2（internal standard）. RESULTS： The linear range of zolpidem， dexzopiclone and zaleplon were 0.02-20.00， 0.50-20.00， 0.02-20.00 ng/ml， respectively （r＝0.990 1，0.996 8， 0.991 7）. LLOQ of them were 0.02， 0.50， 0.02 ng/ml， and detection limit were 0.01， 0.20， 0.01 ng/ml. RSDs of intra-day and inter-day were all lower than 15％； extraction recovery were 88.9％-106.5％； matrix effect were 94.8％-106.3％. CONCLUSIONS： The method is simple， rapid， sensitive and specific， and it can be used for simultaneous determination of zaleplon， zolpidem and dexzopiclone in human plasma.