Aims Nitrogen (N) fertilization is known to modify a plant’s susceptibility to necrotrophic diseases. However, the effect of N nutrition on defence is not well known. It was hypothesized that not only molecules related to the N metabolism but also main sugars could mediate the effect of plant fertilization on its susceptibility to pathogens. Methods Two necrotrophic fungi, Botrytis cinerea and Sclerotinia sclerotiorum were inoculated on leaves of lettuce plants grown at five nitrate (NO3 −) fertilization levels, in three independent experiments. Variations in plant composition at the time of inoculation were linked to the size of lesions observed after 5–6 days. Results Both diseases were favoured by high NO3 − fertilization. However, the highest disease levels were not found in the same experiment for B. cinerea and S. sclerotiorum. Among the components measured, NO3 − and sucrose (SUC) were positively and negatively correlated to the two diseases in the three experiments, but the relationship between SUC and lesion size was more significant for S. sclerotiorum. Water content, N and total carbon (C) were also significantly correlated to the diseases, but the relationships were less straightforward. The ratios of SUC over total sugars and fructose (FRU) over total sugars fitted, very closely for S. sclerotiorum, a negative and positive exponential relationship respectively with lesion size. Absolute or relative glucose levels were not linked to the diseases. Conclusions Plant metabolic modifications induced by variations of N availability conferred the plant variable defence ability, which seemed, at least for S. sclerotiorum, mainly mediated by variations in host SUC and FRU levels. The generalization of these findings to other species would be of interest.