N,N-diethyl-meta-toluamide (DEET) is the active ingredient in many insect repellants against biting insects such as mosquitoes and ticks. It is one of the few micro-pollutants that are increasingly found in natural waters. The fact that DEET occurs in both influent and effluent of wastewater treatment works is indicative of its refractory nature. This work investigates the reactions of DEET with ozone, an oxidant that is becoming more common in treatments and disinfections of wastewater and drinking water. The transformation pathways were mapped, and a reaction model that accurately predicts the reactions was developed. The ozonation of DEET did not decrease the bioactivity of treated water, but instead resulted in a twofold increase in the microtoxicity. The findings suggest that the products of DEET ozonation has greater toxicity potentials compared to the parent compound posing a real hazard to human health and environment.