The dataset includes water-quality sensor readings collected by the U.S Geological Survey (USGS) from the Caloosahatchee River at the Franklin Lock and Dam and 12 open-air fiberglass tanks filled with Caloosahatchee River water used for mesocosm experiments testing the effects of elevated nutrients on harmful algal bloom (HAB) dynamics. This dataset contains water quality sensor readings from two of eight total independent experiments conducted from June 8-11, 2020 and September 14-17, 2020. Each of the 12 tanks were randomly treated with either ammonium hydroxide, sodium nitrate, sodium phosphate, or left untreated (controls) for a total of three replicates of each treatment. The tanks were treated with incrementally higher dosing solutions every 24 hours for the first three days of the four-day experiment (T0, T24, and T48). Biological and nutrient concentration samples were collected each day before and after the dosing solution was applied and at T72, the final day of the experiment. Water-quality sensor data were collected on all four days (T0, T24, T48, T72) at three depths within each tank and the river using a multi-parameter water-quality sonde before the dosing solutions were applied. Each point reading is provided as an instantaneous measurement. Water-quality parameters measured include chlorophyll fluorescence, dissolved oxygen, fluorescence of dissolved organic matter, pH, phycocyanin fluorescence, specific conductance, turbidity, and water temperature. The data is provided as a table in comma delimited format.