Marine sponges often harbor an abundance of associated organisms. We characterized mesofauna associated with the common tropical sponge Amphimedon viridis, and then tested whether physical (spicules) or chemical (lipophilic or hydrophilic extracts) properties of this sponge provide a prospective refuge for mesofauna from fish predation. Sponge analyses revealed a moderately diverse and numerically rich community of sponge-associated mesofauna comprised primarily of mesocrustaceans (82% of total fauna). Eighty-nine percent of these were amphipods, but smaller numbers of tanaids, decapods, and isopods also occurred. Quantitative sampling of outer surfaces and interstices of fifteen A. viridis yielded a total mean ± 1 SD density of sponge-associated mesofauna of 53 ± 9.3 individuals per 100 cm3 wet sponge tissue. Among the numerically dominant amphipods, 65% occurred on outer sponge surfaces where they are most vulnerable to fish predators. We evaluated whether A. viridis provides a prospective refuge from predation by assessing the palatability of this sponge to the sympatric generalist pinfish Lagodon rhomboides. When presented small (2 mm) bite-size pieces of whole sponge tissue, similar in size to what fish might incidentally ingest should they attempt to consume sponge-mesofaunal associates, pinfish displayed strong feeding deterrence. Alginate food pellets containing tissue-level concentrations of sponge spicules caused a weak but significant deterrent response. In contrast, alginate pellets containing tissue-level concentrations of either lipophilic or hydrophilic extracts of A. viridis were highly deterrent to pinfish. Thus, chemical, and to a considerably lesser degree, physical defenses (spicules) may contribute to this sponge serving as a protective refuge for associated mesofauana. © 2008 Elsevier B.V. All rights reserved.