AbstractPlasma activation of liquids or cell cultures is a method for investigating the consequences of plasma produced reactive oxygen and nitrogen species (RONS) on living systems. The reproducible transfer of RONS, ions, electrons, and photons to the liquid is critical for determining reaction mechanisms and biological outcomes, and depends strongly on system parameters. A common in vitro method of plasma treatment of cells is a plasma jet directed into a well plate filled (or partially filled) with a liquid cell growth media. This method of treatment intrinsically has several environmental and geometrical factors that could lead to variability in the activation of the media. Uncontrolled or unreported geometrical and environmental factors that affect this transfer can, therefore, influence the reproducibility of measurements. In this paper, results from a numerical modeling investigation of a pulsed helium plasma jet interacting with water in a well plate are discussed while varying the height of the well‐plate rim. The height of the rim changes gas flow patterns, the ratio of He‐to‐air, and the water vapor content in the gas layer above the liquid. With a low rim, gas flowing from the jet stagnates on‐axis and flows radially outward with few vortices that recirculate reactants. With high rims, the gas flow is dominated by vortices and recirculation. With a low rim, the ionization wave (IW) from the jet strikes the liquid and proceeds as a surface IW across the water. With higher rims, the densities of helium and water vapor are higher above the liquid, which results in a volumetric propagation of the IW, initially producing higher densities of H2, HO2, OH, and H2O2. The end result is that for otherwise identical conditions, the densities of solvated H2O2aq and select reactive nitrogen species increase with rim height due to the vortices that recirculate reactants.