A rising concern to lake and reservoir water quality is pharmaceuticals and personal care products (PPCPs), which are increasingly ubiquitous in the environment. Many studies have examined the introduction of PPCPs to freshwater ecosystems through wastewater treatment, but less is known about how direct human interactions, such as swimming, may influence PPCP concentrations. We sampled PPCPs before and after an unprecedented whole-ecosystem manipulation in a large drinking water reservoir in Roanoke, Virginia located in a forested catchment: a 1.9 km swimming race with approximately 1600 swimmers. Importantly, no swimmers have ever been allowed to swim in the reservoir prior to the race, enabling a unique opportunity for assessing the direct effect of swimmers on PPCPs. We monitored six sampling sites across the reservoir based on the swimming race course and the water outtakes for treatment five days prior to the race, the day of the race, and three days after the race. On each day, we collected near surface water samples at all six sites for PPCPs (acetaminophen, caffeine, and triclosan), nutrient concentrations (ammonium, nitrate, and soluble reactive phosphorus), phytoplankton, water temperature, dissolved oxygen, pH, and total dissolved solids. We also sampled for total coliform and E. coli bacteria. Despite being located in a forested catchment with no swimmers, we observed low but detectable levels of acetaminophen, caffeine, and triclosan prior to the race. Acetaminophen and triclosan increased after the race day, with some sites exceeding our limit of quantification by the final sampling day. E. coli concentrations were low prior to the race and remained low after, except at the race finish site, where concentrations increased from 1 to 58 CFU/100mL. Nutrient concentrations, dissolved oxygen, pH, and total dissolved solids all remained consistent before and after the race. Our results show that swimming in reservoirs can lead to increases in concentration of PPCPs, though concentrations remained at trace levels.