Objective To develop a method for the determination of 12 organophosphate esters (OPEs) fire retardants in honey by ultra-high-performance liquid chromatography-high-resolution mass spectrometry. Methods The samples were enriched, extracted and cleaned-up by a sugar-induced acetonitrile-water liquid-liquid extraction system, eluted with a gradient of methanol-formic acid-water, and then separated on a HSS T3 chromatographic column (2.1 mm×100 mm, 1.8 μm). The analytes were determined by high-resolution mass spectrometry in the targeted single-ion monitoring mode, with the quantification by internal standard method. Results The linearity of the 12 OPEs, with R2 > 0.99, was observed from 0.2 to 20 μg/L, while the range of the LODs and the LOQs were 0.05 - 0.3 μg/kg and 0.1 - 0.9 μg/kg, respectively. Recoveries of the 12 OPEs at three different spiked levels ranged from 86.2% to 119.5%, with RSDs ranging from 1.24% to 8.16%. Analysis of 16 honey samples revealed 100% detection of TPhP at concentrations ranging from 1.7 to 11.8 μg/kg and 50% detection of TEP at levels from LOD to 1.5 μg/kg. Conclusion The method is convenient, reproducible, sensitive and suitable for the trace determination of OPEs in honey.