Ulva sp. infection in seaweed is considered one of the most harmful infections, since it penetrates deep into the host cell wall and disorganizes the cortical tissue. In Gracilaria chilensis farms, epiphytism is one of the major biological problems and strong fluctuations in landings of this rhodophyte have been documented in the past decades. The present study evaluated the damage of Ulva sp. infection through histological assessment, germination of the epiphytic algal spores on G. chilensis, the photosynthetic response, and gene expression associated with stress after exposure to epiphyte infection. The histological results showed significant and a characteristic damage according to the type of infection described by this species. In addition, a higher infection in farmed than in natural individuals was observed, along with increased photoinhibition of the maximum fluorescence quantum yield (Fv/Fm). Two genes, one related to photosynthesis (PSBO) and the other responsible for neutralizing free superoxide radicals (SOD-C), followed the same pattern, although due to the high variance no significant differences were detected. VBPO, a gene related to the halo-organic compounds synthesis, showed a higher expression in infected thalli, independent of the population type, suggesting a higher protection of the alga from oxidative damage. This study confirms the sensibility of farmed populations of G. chilensis to infection by Ulva sp. and the existence of an active response to early infection.