Iodinated X-ray contrast media (ICM) are a group of tri-iodinated aromatic compounds used in medical imaging of soft tissues. They are regarded as emerging contaminants, and widely detected in the effluents of wastewater treatment plants, surface water, and groundwater. In the present study, degradation of iohexol, a typical ICM agent, was systematically investigated in a Co2+ activated peroxymonosulfate (Co2+/PMS) oxidation process at neutral conditions. Experimental data revealed that the apparent rate of iohexol degradation was first-order with respect to the concentrations of both Co2+ and PMS. SO4 center dot- was found to induce the oxidative degradation of iohexol primarily. Presence of humic acid (HA) significantly inhibited the iohexol degradation, while the influence of Cl- was negligible. A total of 11 intermediates were identified by HPLC-MS/MS and three transformation pathways, i.e., cleavage of side chain, H-abstraction from side chain, and oxidative deiodination, were proposed. The degradation started with the oxidation of the side chains in iohexol molecule and followed by deiodination on the aromatic ring. Following the degradation of iohexol, formation of free iodine and iodinated disinfection byproducts (I-DBPs) was found. When 50 mu M was treated with 1mM PMS and 1 mu M Co2+, the yields of iodoform and triiodoacetic acid reached 38.12 and 577.99 mu g/L, respectively, in 12 h. In addition, the formation of I-DBPs was prominently enhanced by the presence of HA. Because I-DBPs are highly toxic, this study suggests the potential risks when SO4 center dot- is applied to degrade ICM compounds.