The non-covalent complexes of α-, or β-cyclodextrins (α-, β-CD) with the newly developed antidepressant compound, SIPI5838, have been investigated. The complexes of α-, or β-CD with SIPI5838 have been prepared and characterized by electrospray ionization mass spectrometry (ESI-MS), and ultraviolet (UV) spectrometry as well. The mass spectrometry results revealed that SIPI5838 (guest) and α-, or β-CD (host) formed a 1∶1 complex in aqueous solution. The formation of the non-covalent complexes could significantly increase the solubility of SIPI5838 in aqueous solution. Furthermore, α-/β-CD-SIPI5838 complexes exhibited different features and properties in UV-Vis spectroscopy from the reactants, which confirms the results of ESI-MS. The formation constant of the complexes have also been estimated by phase solubility studies. The calculated apparent formation constants of SIPI5838-β-CD and SIPI5838-α-CD are 1.83×103 and 3.15×101 mol－18226;L, respectively. The stability of these two complexes are in the order of β-CD-SIPI5838＞α-CD-SIPI5838.