Serotonin (5-HT), an important molecule in metazoans, is involved in a range of biological processes including neurotransmission and neuromodulation. Both its creation and release are tightly regulated, as is its removal. Multiple neurochemical pathways are responsible for the catabolism of 5-HT and are phyla specific; therefore, by elucidating these catabolic pathways we glean greater understanding of the relationships and origins of various transmitter systems. Here, 5-HT catabolic pathways were studied in Strongylocentrotus purpuratus and Xenoturbella bocki, two organisms occupying distinct positions in deuterostomes. The 5-HT-related compounds detected in these organisms were compared with those reported in other phyla. In S. purpuratus, 5-HT-related metabolites include N-acetyl serotonin, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid; the quantity and type were found to vary based on the specific tissues analyzed. In addition to these compounds, varying levels of tryptamine were also seen. Upon addition of a 5-HT precursor and a monoamine oxidase inhibitor, 5-HT itself was detected. In similar experiments using X. bocki tissues, the 5-HT-related compounds found included 5-HT sulfate, gamma-glutamyl-serotonin and 5-hydroxyindole acetic acid, as well as 5-HT and tryptamine. The sea urchin metabolizes 5-HT in a manner similar to both gastropod mollusks, as evidenced by the detection of gamma-glutamyl-serotonin, and vertebrates, as indicated by the presence of 5-hydroxyindole acetic acid and N-acetyl serotonin. In contrast, 5-HT metabolism in X. bocki appears more similar to common protostome 5-HT catabolic pathways.