Cryptocaryon irritans is a pathogenic ectoparasitic ciliate that infects marine teleosts, causing massive mortality and economic losses in aquaculture. Ultraviolet light (UV) and ozone (O3) are commonly used for disinfection in factory aquaculture; however, the efficacy of neither method against C. irritans had been evaluated. This study aimed to evaluate the efficacy of UV and ozone in destroying C. irritans. UV or ozone treatment changed or ruptured the shape of C. irritans theronts, although C. irritans tomonts showed some resistance. The minimum in vitro lethal doses of UV and ozone against theronts were 2.88× 105 μWs/cm2 and 0.15 mg/L, respectively. In vivo, UV and ozone-treated theronts lost their ability to infect pompano (Trachinotus ovatus) when exposed to doses above 1.84 × 105 μWs/cm2 and 0.10 mg/L, respectively. Unexpectedly, exposure to low ozone levels (< 0.04 mg/L) enhanced theronts infecting ability. These results provide a reference for C. irritans theronts disinfection in factory aquaculture and further studies on C. irritans.