This study investigated the efficacy of low-dose ozone microbubble solution and conventional aqueous ozone as inactivation agents against Tulane virus samples in water over a short period of time. Noroviruses are the primary cause of foodborne illnesses in the US, and the development of effective inactivation agents is crucial. Ozone has a high oxidizing ability and naturally decomposes to oxygen, but it has limitations due to its low dissolution rate, solubility, and stability. Ozone microbubbles have been promising in enhancing inactivation, but little research has been done on their efficacy against noroviruses. The study examined the influence of the dissolved ozone concentration, inactivation duration, and presence of organic matter during inactivation. The results showed that ozone microbubbles had a longer half-life (14 ± 0.81 min) than aqueous ozone (3 ± 0.35 min). After 2, 10, and 20 min postgeneration, the ozone concentration of microbubbles naturally decreased from 4 ppm to 3.2 ± 0.2, 2.26 ± 0.19, and 1.49 ± 0.23 ppm and resulted in 1.43 ± 0.44, 0.88 ± 0.5, and 0.68 ± 0.53 log₁₀ viral reductions, respectively, while the ozone concentration of aqueous ozone decreased from 4 ppm to 2.52 ± 0.07, 0.43 ± 0.05, and 0.09 ± 0.01 ppm and produced 0.8 ± 0.28, 0.29 ± 0.41, and 0.16 ± 0.21 log₁₀ reductions against Tulane virus, respectively (p = 0.0526), suggesting that structuring of ozone in the bubbles over the applied treatment conditions did not have a significant effect, though future study with continuous generation of ozone microbubbles is needed.