A series of six caffeic acid derivatives (1–6) in Osmanthus yunnanensis were investigated by electrospray quadrupole time-of-flight tandem mass spectrometry (ESI-QToF-MS/MS) in both negative- and positive-ion modes. High-quality MS/MS spectra of [M + H]⁺ are generated from high-abundance protonated parent ions obtained by addition of ammonium chloride to the solutions. Fragmentation mechanisms of [M – H]⁻ and [M + H]⁺ precursor ions were proposed and elemental compositions of most of the product ions were confirmed on the basis of the high-resolution ESI-collision-induced dissociation (CID)-MS/MS spectra. It was found that the fragment ions at m/z 179, m/z 161, m/z 135 and m/z 134 in negative-ion mode and at m/z 163, m/z 145 and m/z 135 in positive mode should be the characteristic ions of caffeic acid. In addition, the radical fragment ions with high abundance were observed for many caffeic acid derivatives especially for 4. The structural elements of unknown compounds 7 and 8 were tentatively identified on based on tandem mass spectra of known ones.