Although isocarbophos is a widely used insecticide, its toxicity to aquatic organisms has not been well characterized. In this study, zebrafish were exposed to isocarbophos at concentrations of 50 mu g L-1 and 200 mu g L-1 to assess its bioaccumulation, metabolic disruption, and oxidative stress. Metabolomics analysis based on H-1 NMR spectroscopy showed that 50 mu g L-1 and 200 mu g L-1 isocarbophos exposure induced increases in leucine, isoleucine, valine, and alanine compared to levels in the control. Lactate, creatine, and taurine were reduced in the 50 mu g L-1 isocarbophos exposure group, and only lactate decreased in response to 200 mu g L-1 isocarbophos. After zebrafish were exposed to 50 and 200 pg isocarbophos for 28 days, the activities of antioxidant en- zymes (SOD, CAT, and GPx) and GSH contents decreased significantly in the liver. This result indicates that there was significant oxidative stress in the liver. Furthermore, changes in metabolite profiles significantly covaried with changes in several oxidative stress endpoints based on partial least squares regression. These results will contribute to the environmental risk assessment of isocarbophos and clarify the mechanism underlying its toxicity in zebrafish.