Somatostatin (SST) and cortistatin (CST) are neuromodulators with distinct expression patterns and functions. While SST and CST have been extensively studied in mammalian central nervous system (CNS) and immune system, their roles in teleost fish remain poorly explored due to evolutionary emergence of multiple SST paralogous genes. This study aimed to identify SST isoforms in gilthead seabream (Sparus aurata) and assess their transcriptional levels. Phylogeny and synteny analyses reclassified the six SST genes and proteins as SST1, SST3, SST3-like, SST4, SST5, and SST6. The protein sequences showed high conservation, except for an additional region upstream of the SST3-like protein's leader region. Evolutionary differences were mainly due to specific amino acid residue changes in the mature peptide. Genetic analyses revealed constitutive expression of five genes (sst1, sst3, sst5, sst4 and sst6) in all studied organs, except for sst3 in the heart, liver, and blood. The highest expression of sst1, sst3, sst4 and sst6 genes occurred in the brain's forebrain, while sst5 was most expressed in the heart. However, sst4 exhibited very low basal expression across all analysed tissues. In vitro, λ-carrageenan and cantharidin upregulated sst6 transcription in head kidney leucocytes (HKLs), indicating a potential anti-inflammatory role similar to mammalian CST. Additionally, sst5 expression was downregulated during the innate cell-mediated cytotoxic response, suggesting a regulatory role. These findings provide insights into the SST/CST gene family in gilthead seabream, necessitating gene and protein reclassification, and underscore their significant neuroendocrine and immune system functions, relevant for teleost research.