The use of nematodes as biological indicators of environmental quality was evaluated in sediments of the Mediterranean Sea. The Shannon-Diversity Index (H′), the Maturity Index, the c-p%, the Index of Trophic Diversity (ITD) and the presence of sensitive/tolerant genera were applied at a Mediterranean scale to 12 different coastal sites and used to identify the five classes of ecological quality status assessed according to the Water Framework Directive. The results revealed that nematodes represent a highly informative assemblage. In particular, the presence/absence of specific genera indicators, followed by c-p% composition and H′, can be used to evaluate the ecological quality status efficiently.