Fascioliasis is caused by two species of trematodes that mainly affect the liver. It belongs to the group of foodborne disease infections. It is a zoonotic disease, while anaplasmosis is a tick-borne disease. Both diseases occur worldwide, particularly in regions with intensive animal production. Therefore, the current study aimed to investigate the incidence rate of Fasciola and Anaplasma infections among cattle and buffalo in a part of southern Egypt,“Qena province,” in different seasons among male and female animals with special reference to the harmful effects of Fasciola in the liver of infected animals. The study was carried out from January 2020 to January 2021. A total of 437 cattle and 188 buffaloes of mixed breeds with an age range from 1 to 3 years were selected randomly for the study. Fecal samples were obtained and analyzed for the presence of fluke eggs using direct smear, flotation, and sedimentation techniques. Samples of liver fluke were collected from the liver of slaughtered animals for histopathology. The results revealed that fascioliasis incidence among cattle and buffalo in Qena was 3.43 and 4.26%, respectively. The microscopic examination of blood smears from cattle and buffaloes revealed that 7.5% had an Anaplasma infection; in addition, the infection rate concerning gender indicated that it was higher in females 7.57% than males 6.67%. The findings of fascioliasis and anaplasmosis in farm animals indicate that the danger of both diseases in farm animals, which affects the economic production of animals, increases the risk of infection with zoonotic agents for farmworkers.