Combustion-generated particles released into the atmosphere undergo reactions with oxidants, which can change the particles' physiochemical characteristics. In this work, we compare the physical and chemical properties and cellular response of particles fresh from a flame with those oxidized by ozone and nitrogen dioxide. The reaction with ozone and nitrogen dioxide does not significantly modify the physical characteristics of the particles (primary particle size, fractal dimension, and surface area). However, oxidation affects the chemical characteristics of the particles, creating more oxygen and nitrogen containing functional groups, and increases their hydrophilicity. In addition, oxidized soot generates more reactive oxygen species, as measured by the dithiothreitol (DTT) assay. Furthermore, oxidized soot is 1.5–2 times more toxic than soot that was not reacted with ozone, but the inflammatory response, measured by interleukin-8 (IL-8) secretion, is unchanged. These results imply that combustion-generated particles released into the atmosphere will have an increased toxicity on or after high ozone days.