Helminth infections are among the most prevalent neglected tropical diseases, causing an enormous impact in health and the socioeconomic status of developing countries. The study host-parasite interactions constitute a promising approach for developing new tools to control these infections. Echinostoma caproni is an extensively used model to study host–parasite interactions with emphasis on the factors determining the course of the infections. Herein, we study how infection-induced changes influence host susceptibility and pathology by a proteomic approach.