Adverse health effects due to exposure to particulate matter (PM) are among the most important global environmental health risks. However, the effects of exposure to secondary organic aerosols (SOA), a major component of the global aerosol, are largely unknown. Here we exposed lung epithelial cells (A549) to fresh and aged SOA particles and investigated the effect of SOA atmospheric aging on cell viability and gene expression. Naphthalene-and α-pinene-derived SOA were formed in an oxidation flow reactor that simulates atmospheric SOA formation and aging dominated by OH radical oxidation under NO x -free conditions. The SOA mass and chemical composition were characterized on-line using a scanning mobility particle sizer and aerosol mass spectrometer. Fresh and aged SOA were directed to an air−liquid interface cell exposure system. Aged naphthalene-and αpinene-derived SOA were somewhat more toxic than fresh SOA. Aged naphthalene SOA contained peroxide levels that were higher than those of fresh SOA. The level of induction of Nrf2 signaling increased following exposure to aged naphthalene SOA. Given the global prevalence of SOA and its observed toxicity, this study calls for more studies aimed at understanding the underlying mechanics.