The impact of fish and oysters on components of the pelagic microbial food web (MFW) was studied in a 10 d mesocosm experiment using Mediterranean coastal waters. Two mesocosms contained natural water only ('Controls'), 2 contained natural water with Crassostrea gigas ('Oyster'), and 2 contained natural water with Atherina spp. ('Fish'). Abundances and biomasses of microorganisms (viruses, bacteria, phytoplankton, heterotrophic flagellates, and ciliates) were measured to estimate their contribution to the total microbial carbon biomass. Two MFW indices, the microbial autotroph: heterotroph C biomass ratio (A:H) structural index and the gross primary production: respiration ratio (GPP:R) functional index, were defined. In the Fish mesocosms, selective predation on zooplankton led to a trophic cascade with 51% higher phytoplankton C biomass and consequently higher A: H and GPP: R than in the Controls. By the end of the experiment, the Oyster mesocosms had a bacterial C biomass 87% higher and phytoplankton C biomass 93% lower than the Controls, giving significantly lower A: H and GPP: R (<1). Overall, the results showed that wild zooplanktivorous fish had a cascading trophic effect, making the MFW more autotrophic (both indices >1), whereas oyster activities made the MFW more heterotrophic (both indices <1). These MFW indices can therefore be used to assess the impact of multiple local and global forcing factors on the MFW. The results presented here also have implications for sustainable management of coastal environments, suggesting that intense cultivation of filter feeders can be coupled with management to encourage wild local zooplanktivorous fishes to maintain a more resilient system and preserve the equilibrium of the MFW.