The aim of this work is to underline the biological significance of mitochondrial uncoupling proteins (UCPs) in ectothermic fish using the gilthead sea bream (Sparus aurata L.) as an experimental model. A contig of 1,990 bp in length was recognized as a UCP1 ortholog after initial searches in the gilthead sea bream AQUAFIRST database ( http://www.sigenae.org/aquafirst ). Additional searches were performed in skeletal muscle by RT-PCR, and the amplified PCR product was recognized as UCP3 after sequence completion by 5'- and 3'RACE. UCP1 expression was mostly detected in liver, whereas UCP3 transcripts were only found in skeletal and cardiac muscle fibres (white skeletal muscle > red skeletal muscle > heart). Specific gene regulation of UCP1 (liver) and UCP3 (white skeletal muscle) was addressed in physiological models of age, seasonal growth and energy-metabolic unbalances. Both the increase in energy demand (stress confinement) and the reduction in energy supply during adaptive cold response in winter down-regulated UCP1 expression. Conversely, transcript levels of UCP3 were higher with age, seasonal fattening and dietary deficiencies in essential fatty acids leading to the increase in fatty acid flux towards the muscle. This close association between UCP1 and UCP3 with the oxidative and metabolic tissue status is perhaps directly related to the ancestral protein UCP function, and allows the use of UCPs as lipotoxicity markers in ectothermic fish.