Tropical coral reefs are characterized by low-nutrient waters that support oligotrophic picoplankton over a productive benthic ecosystem. Nutrient-rich effluent released from aquaculture facilities into coral reef environments may potentially upset the balance of these ecosystems by altering picoplankton dynamics. In this study, we examined how effluent from a prawn (Litopenaeus vannamei) farming facility in Al Lith, Saudi Arabia, impacted the inorganic nutrients and prokaryotic picoplankton community in the waters overlying coral reefs in the Red Sea. Across 24 sites, ranging 0-21 km from the effluent point source, we measured nutrient concentrations, quantified microbial cell abundances, and sequenced bacterial and archaeal small subunit ribosomal RNA (SSU rRNA) genes to examine picoplankton phylogenetic diversity and community composition. Our results demonstrated that sites nearest to the outfall had increased concentrations of phosphate and ammonium and elevated abundances of non-pigmented picoplankton (generally heterotrophic bacteria). Shifts in the composition of the picoplankton community were observed with increasing distance from the effluent canal outfall. Waters within 500 m of the outfall harbored the most distinct picoplanktonic community and contained putative pathogens within the genus Francisella and order Rickettsiales. While our study suggests that at the time of sampling, the Al Lith aquaculture facility exhibited relatively minor influences on inorganic nutrients and microbial communities, studying the longer-term impacts of the aquaculture effluent on the organisms within the reef will be necessary in order to understand the full extent of the facility’s impact on the reef ecosystem.