Understanding how fish with divergent energy reserve profiles respond to feed deprivation is critical for optimizing aquaculture feeding strategies. In this study, we compared two rainbow trout (Oncorhynchus mykiss) lines selected for low (lean, L) or high (fat, F) muscle lipid content. Both lines underwent a 3-week starvation period followed by 3 weeks of refeeding using self-feeders. The L line exhibited faster post-refeeding growth, higher post-refeeding weight gain, and earlier feeding activity concentrated in the morning. Conversely, the F line showed greater weight loss during starvation, reduced haematocrit and innate immune parameters, and limited metabolic recovery. Starvation induced distinct changes in lipid and protein metabolism, hydromineral regulation, and immune responses, with the F line being more metabolically and immunologically impacted. Plasmatic concentrations of calcium and sodium decreased, while chlorides concentrations increased transiently. Principal Component Analysis revealed stronger physiological disruption in the F line during starvation. These findings highlight how fat reserves influence recovery from nutritional stress, offering perspectives for genotype-specific feed management in aquaculture.