Infection of rainbow trout with the parasitic ciliate Ichthyophthirius multifiliis induces a stress response which can be monitored by serum cortisol measurements reflecting involvement of the pituitary-interrenal cell axis in parasite infected fish. Molecular mechanisms associated with the stress response have been less well elucidated - especially with regard to stress effects on metabolism and growth in infected gills – which is the focus of the present study. A controlled experimental infection was performed followed by serum and gill sampling at day 8 post-infection. The stress reactions in the fish were elucidated by measurements of serum cortisol and lysozyme activity, and expression in gills of genes associated with stress, metabolism, and growth. Infection induced a marked elevation of serum cortisol and lysozyme levels, and major changes of metabolic processes in gills. A number of key genes involved in stress (hsps, foxo, saa) and energy metabolism (cyps, pfkfb3, rrm2, mthfd1l) were activated in response to infection whereas several central genes related to growth factors (wnt7a, igfbp7, insr, fgf7, tgfb3, tgfbr1, tgfbr3) were suppressed. A number of potential transcription factors including myc, e2f1, stat1, jun, e2f2, e2f3, and gli2 were found associated with regulation of genes in gills during infection. Mechanisms linking infection of mucosal surfaces and systemic responses are discussed.