The use of atmospheric pressure plasma jets (APPJs) in plasma medicine have produced encouraging results in wound treatment, surface sterilization, deactivation of bacteria, and treatment of cancer cells. It is known that many of the reactive oxygen and nitrogen species produced by the APPJ are critical to these processes. Other key components to treatment include the ion and photon fluxes, and the electric fields produced in cells by the ionization wave of the APPJ striking in the vicinity of the cells. These relationships are often complicated by the cells being covered by a thin liquid layer—wet cells. In this paper, results from a computational investigation of the interaction of APPJs with tissue beneath a liquid layer are discussed. The emphasis of this study is the delivery of electric fields by an APPJ sustained in He/O2 = 99.8/0.2 flowing into humid air to cells lying beneath water with thickness of 200 μm. The water layer represents the biological fluid typically covering tissue during treatment. Three voltages were analyzed—two that produce a plasma effluent that touches the surface of the water layer and one that does not touch. The effect of the liquid layer thickness, 50 μm to 1 mm, was also examined. Comparisons were made of the predicted intracellular electric fields to those thresholds used in the field of bioelectronics.