Haloacetamides (HAcAms) as a new class of nitrogenous disinfection byproducts (N-DBPs) have been widely detected in drinking water and reclaimed water. Cytotoxicity and genotoxicity of monoHAcAms are determined by the leaving tendency of the halogens and decrease following a rank order of iodoacetamide (IAcAm)>bromoacetamide (BAcAm)≫chloroacetamide (CAcAm). However, the in vivo toxicity date for monoHAcAms is limited. In this study, hepatic oxidative stress and metabolomics responses in mice corresponding to monoHAcAms exposure were investigated. Exposure to the monoHAcAms decreased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the levels of malonaldehyde (MDA) and increased the level of 8-hydroxy-2-deoxyguanosine (8-OHdG), indicating that each exposure generated oxidative stress in mice liver. Metabolomic alterations were also induced by each monoHAcAms exposure. In addition, disruptions of metabolic pathways, related to amino acid, energy and lipid metabolism, were identified based on the significantly changed metabolites. These data, for the first time, provide a comprehensive view for the toxic effects of monoHAcAms.