The physiological consequences of the activation of the immune system in fish are not well understood. In particular, skeletal muscle, due to its essential role in locomotion and whole-animal energy homeostasis, is a potentially important target of inflammation. In this study, we have evaluated the in vivo effects of lipopolysaccharide (LPS) on the white and red skeletal muscle transcriptome of the gilthead seabream (Sparus aurata) by microarray analysis at 24 and 72 h after injection. In white muscle, the transcriptomic response was characterized by an up-regulation of genes involved in carbohydrate catabolism and protein synthesis at 24 h and a complete reversal of this pattern at 72 h. In red muscle, an up-regulation of genes involved in carbohydrate catabolism and protein synthesis was observed only at 72 h after LPS administration. Interestingly, both white and red muscles showed a similar consistent down-regulation of immune genes at 72 h post-injection. However, genes involved in muscle contraction showed a general up-regulation in response to LPS in both types of muscle. In summary, LPS administration causes muscle type-specific responses regarding the expression of genes involved in carbohydrate and protein metabolism and a common decreased expression of immune genes in skeletal muscle, concomitant with increased expression of genes for contractile elements. Our results evidence a robust and tissue-specific transcriptomic response of the skeletal muscle to an acute inflammatory challenge.