Freshwater ecosystems of Mongolia belong to the three major Central Asian drainage systems: Arctic drainage, Amur River drainage, and Central Asian Internal drainage. The Great Lakes Depression takes considerable part of the latter. One of the few fish species living there, Oreoleuciscus potanini, is the most common and widespread endemic species in the Central Asian region. Parasitological surveys on O. potanini from the Great Lakes Depression have not occurred regularly in recent years. Consequently, this study was conducted to explore the species diversity of helminth parasites in O. potanini in the three lakes of Khar Us Nuur National Park. In total, 52 O. potanini specimens were collected from the lakes Khar, Khar Us and Durgen and sampled in August 2012. In addition to the parasites, the age and diet spectrum of the fish species were studied. The fish were examined for infection with ecto- and endo- macroparasites. The species composition of Diplostomum spp. metacercariae from the eyes of fish was investigated using a molecular approach. In the lakes Khar and Khar Us the fish age ranged from four to 32 years old and from eight to 35 years old, respectively. Fish of four age groups (9, 10, 11 and 14 years old) were in Lake Durgen. Algae and various insects, including Chironomida larvae were the main food of the O. potanini in all three lakes. When the diet was investigated we found that in Lake Durgen Cladocera crustaceans were the significant component in the fish diet, and no fish was found in the O. potanini diet there. During the study 26 parasites species were identified from the three lakes. The total fauna is represented by four phyla, including Acanthocephala (one species), Annelida (one species), Nematoda (four species), Platyhelminthes (20 species). The last group was the most numerous and diverse, including three species of Cestoda, six species of Monogenea and 11 species of Trematoda. Five species of parasites were specific to O. potanini only (monogeneans Gyrodactylus mongolicus, G. oreoleucisci, G. pewsowi, nematodes Philometra oreoleucisci and Rhabdochona humili). The other helminthes exhibited a low host-specificity, infecting a wide range of fishes in the Holarctic. The larvae of endohelminthes predominate in the parasite fauna. The majority of these parasites enter the fish via various invertebrate species during O. potanini's feeding. Our study provided novel data on the species diversity of Diplostomum spp. metacercaria in O. potanini's eyes. They were represented by three species: Diplostomum spathaceum, D. pseudospathaceum and Diplostomum sp. LIN2. The species richness and diversity of parasites were much higher for O. potanini from the lakes Khar and Khar Us (26 species), than that for O. potanini of Lake Durgen (15 species). The possible reason for the absence of some parasites in Lake Durgan is an increased water salinity. It is likely that, despite the potential for the fish to exist under conditions of an elevated salinity, parasites (or their invertebrate hosts) are not adapted to it. Our findings clarified the known parasite diversity in lakes of the Khar Us Nuur National Park, indicating that the Great Lakes Depression ecosystem may be characterised by many unique parasite assemblages. The results of investigation on the parasitic fauna of O. potanini confirm a review of the evolutionary youth of this fish group.