Serum amyloid A (SAA) is a family of acute-phase proteins, recognized as important effectors of innate immunity in higher vertebrates. Under pro-inflammatory conditions, up-regulation of saa transcripts occurs not only in the liver, but also in several extrahepatic tissues of a wide variety of vertebrates. SAA is also known as the precursor to amyloid A (AA), a major component of amyloid fibrils deposited in liver, kidney and spleen of humans suffering chronic inflammatory diseases. Here we show the up-regulation of saa transcription in lesions affecting skin, adipose tissue and skeletal muscle of rainbow trout naturally and experimentally infected with Flavobacterium psychrophilum, the causative agent of cold water disease (CWD). Using an antiserum against a trout acute SAA peptide that was previously shown to specifically recognize intact recombinant trout SAA and peptides derived from it, we showed by confocal microscopy analysis extensive colocalization of SAA and thioflavin T (ThT) staining in the skeletal muscle fibers of infected fish, suggesting for the first time the presence of AA-derived aggregates in the skeletal muscle of a lower vertebrate. These findings support the idea that SAA and/or its derivatives could constitute relevant markers for fish health and also for fish meat quality control.