To examine the grazing effects of copepod-dominated mesozooplankton on heterotrophic microbial communities, four mesocosm experiments using gradients of zooplankton abundance were carried out at a coastal marine site. The responses of different protist groups (nanoflagellates, ciliates) and bacterioplankton in terms of abundance and additionally, for bacteria, diversity, production, and exoenzymatic activity, were monitored during 1 week of incubation. Independent of the initial experimental abiotic conditions and the dominating copepod species, zooplankton caused order-of-magnitude changes in microbial functional groups in a clear community-wide four-link trophic cascade. The strongest predatory effects were observed for protist concentrations, thus generating inverse relationships between mesozooplankton and ciliates and between ciliates and nanoplankton. Copepod grazing effects propagated even further, not only reducing the abundance, production, and hydrolytic activity of bacterioplankton but also increasing bacterial diversity. The overall strength of this trophic cascade was dampened with respect to bacterial numbers, but more pronounced with respect to bacterial diversity and activity. High predation pressure by heterotrophic nanoflagellates, realized at the highest copepod abundance, was probably the underlying mechanism for these structural changes in the bacterial assemblages. Our results thus suggest a mechanism by which changes in higher trophic levels of marine plankton indirectly affect prokaryotic assemblages and microbially mediated ecosystem functions