A metabolomics time-course study was performed in rats to find out early biomarkers and highlight the main metabolic pathways that are significantly altered in first period after acute low doses uranium exposure. A dose response relationship study was established from urine and plasma sample collected periodically during 9 months after exposure of young adult male rats to uranyl nitrate. LC-MS and biostatistical analysis were performed to identify early discriminant metabolites. As expected, low-dose of uranium have time-related non-toxic biological effects from which it was possible to identify early and delayed markers of exposure in both urine and plasma sample. Among the most discriminant early ones, a combination of surrogate markers of uranium exposure was validated with a high predictive performance. In urine, nicotinate-nicotinamide and tryptophan metabolism seems to be among the main biological target of as shown previously for chronic contaminations and completed among others by betaine metabolism. This study can be considered as a proof of concept of the relevance of metabolomics in the field of low dose internal contamination to uranium, to develop predictive diagnostic tests useable for radiotoxicological monitoring.