Growth performance and growth regulatory pathways were examined in juvenile gilthead sea bream fed diets containing largely plant-based ingredients. Four isonitrogenous and isolipidic extruded diets with a low level (20%) of fish meal inclusion were formulated with graded levels of a vegetable oil mixture (17:58:25 of rapeseed: linseed: palm oils) replacing fish oil at 33, 66 and 100% (33VO, 66VO and VO diets). All diets were supplemented with lysine (0.55%) and contained soy lecithin (1%). Daily growth coefficients and feed efficiency over the course of an 11-week trial were almost identical in fish fed the FO, 33VO and 66VO diets. The VO diet reduced feed intake and growth without significant effects in proximate whole body composition, nitrogen or energy retentions. The highest concentration of plasma levels of insulin-like growth factor-I (IGF-I) was found in fish fed the 33VO diet. The lowest concentration was attained in fish fed the VO diet, whereas intermediate values were found in fish fed FO and 66VO diets. An opposite trend was found for circulating levels of growth hormone (GH), probably as a result of a reduced negative feedback inhibition from circulating IGF-I. Hepatic expression of IGF-I and GH receptor type I (GHR-I) was regulated in concert and mRNA levels paralleled plasma levels of IGF-I. Hepatic IGF-II and GHR-II were expressed in a more constitutive manner and no changes at the mRNA level were detected. In the skeletal muscle, IGF-I and GHR-I mRNAs did not vary significantly among groups. By contrast, IGF-II mRNA was up-regulated in fish fed the control diet, whereas the highest amount of GHR-II mRNA was attained in fish fed the 66VO diet. All together, these results suggest different growth compensatory mechanisms mediated by IGF-II and GHR-II at the local tissue level. These new insights prompted us to propose that practical diets low in marine ingredients can be used over the productive cycle of gilthead sea bream when essential fatty acids are supplied above the requirement levels.