Urinary tract infection (UTI) encompasses a variety of clinical syndromes ranging from mild to life-threatening conditions. As such, it represents an interesting model for the development of an analytically based scoring system of disease severity and/or host response. Here we test the feasibility of this concept using (1)H NMR based metabolomics as the analytical platform. Using an exhaustively clinically characterized cohort and taking advantage of the multi-level study design, which opens possibilities for case-control and longitudinal modeling, we were able to identify molecular discriminators that characterize UTI patients. Among those discriminators a number (e.g. acetate, trimethylamine and others) showed association with the degree of bacterial contamination of urine, whereas others, such as, for instance, scyllo-inositol and para-aminohippuric acid, are more likely to be the markers of morbidity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-012-0411-y) contains supplementary material, which is available to authorized users.