Luciobarbus guiraonis (Eastern Iberian barbel) is an endemic fish species restricted to Spain, mainly distributed in the Júcar River Basin District. Its study is important because there is little knowledge about its biology and ecology. To improve the knowledge about the species distribution and habitat requirements, nonlinear modelling was carried out to predict the presence/absence and density of the Eastern Iberian barbel, based on 155 sampling sites distributed throughout the Júcar River Basin District (Eastern Iberian Peninsula). We used multilayer feed-forward artificial neural networks (ANN) to represent nonlinear relationships between L. guiraonis descriptors and variables regarding the physical habitat and biological components (macroinvertebrates, fish, riparian forest). The gradient descent algorithm was implemented to find the optimal model parameters; the importance of the ANN’s input variables was determined by the partial derivatives method. The predictive power of the model was evaluated with the Cohen’s kappa (k), the correctly classified instances (CCI), and the area under the curve (AUC) of the receiver operator characteristic (ROC) plots. The best model predicted presence/absence with a high performance (k= 0.66, CCI= 87% and AUC= 0.85); the prediction of density was moderate (CCI = 62%, AUC=0.71 and k= 0.43). The fundamental variables describing the presence/absence were; solar radiation (the highest contribution was observed between 2000 and 4200 WH/m2), drainage area (with the strongest influence between 3000 and 5.000 km2), and the proportion of exotic fish species (with relevant contribution between 50 and 100%). In the density model, the most important variables were the coefficient of variation of mean annual flows (relative importance of 50.5%) and the proportion of exotic fish species (24.4%). The models provide important information about the relation of L. guiraonis with biotic and abiotic variables, this new knowledge can help develop future studies and management plans for the conservation of this species in the Júcar River Basin District and, potentially, for the conservation of other endemic fish species of Barbus and Luciobarbus in Mediterranean rivers.