The contribution of UV exposure to the etiology of skin cancer and photoaging is undisputed. However, the effect of altering the intensity or dose rate of UV, which varies considerably with geographical location, the time of day or year, and the use of sunscreens, is not understood. In this study, the effect of altering the dose rate of UVA was investigated in the immortalized human keratinocyte cell line, HaCaT. Lowering the dose rate of UVA resulted in increased cytotoxicity, which correlated with increases in both lipid peroxidation and DNA damage. Furthermore, exposure at low dose rate did not appear to reduce the ability of UVA to induce the phenomenon of persistent genomic instability. Pretreatment with the antioxidant vitamin E significantly protected against UVA dose-rate effects observed with respect to lipid peroxidation and survival. Additionally, cell populations irradiated at low dose rate exhibited a shift towards a more pro-oxidant state. Taken together, these observations suggest an oxidative stress mechanism is underlying the UVA dose-rate effect. This study demonstrates that dose rates must be included as a key factor when evaluating the biological effects of UVA, especially considering the concerns, which exist regarding the efficacy and photostability of sunscreens to UVA.