To ensure oil sands process water (OSPW) is suitable for discharge into the environment, advanced water treatment technologies are required. In this study, integrated ozonation-biodegradation was investigated as a potential treatment option for OSPW. The treatment efficiency was evaluated in terms of naphthenic acid (NA) degradation, chemical oxygen demand (COD), carbonaceous Biological oxygen demand (CBOD), and acute toxicity reduction. Degradation of NAs of more than 99% was achieved using a semi-batch ozonation system at a utilized ozone dose of 80 mg/L combined with subsequent biodegradation. The results also show that ozone decreased the amount of COD while increasing the biodegradability of COD. It was noted that the carbon number and number of NA rings influenced the level of NA oxidation. With a utilized ozone dose of approximately 100 mg/L, the ozonated and biodegraded treated OSPW showed no toxic effect towards bacterium Vibrio fischeri. The results of this study indicate that integrated ozonation-biodegradation is a promising treatment technology for OSPW.