This study focuses on the generation and loss of reactive oxygen species (ROS) in low-temperature atmospheric-pressure rf (13.56MHz) He+O 2 +H 2 O plasmas, which are of interest for many biomedical applications. These plasmas create cocktails of ROS containing ozone, singlet oxygen, atomic oxygen, hydroxyl radicals, hydrogen peroxide, and hydroperoxyl radicals, i.e. ROS of great significance as recognized by the freeradical biology community. By means of 1-dimensional fluid simulations (61 species, 878 reactions), the key ROS and their generation and loss mechanisms are identified as a function of the oxygen and water content in the feed gas. Identification of the main chemical pathways can guide the optimization of He+O 2 +H 2 O plasmas for the production of particular ROS. It is found that for a given oxygen concentration, the presence of water in the feed gas decreases the net production of oxygen-derived ROS, while for a given water concentration, the presence of oxygen enhances the net production of water-derived ROS. Although most ROS can be generated in a wide range of oxygen and water admixtures, the chemical pathways leading to their generation change significantly as a function of the feed gas composition. Therefore, care must be taken when selecting reduced chemical sets to study these plasmas.