A field study on prevalence of diseases and on selected water quality parameters was carried out in major catfish cultural areas in the Mekong Delta, Vietnam. A total number of 1,602 samples (1,339 with disease signs and 263 without disease sign) of farmed stripped catfish, Pangasianodon hypophthalmus, were collected over 12 sampling months from July 2018 to June 2019. Four major groups of gross clinical signs were recorded among the diseased fish samples. Ectoparasite infections (Dactylogyrus spp. on the gill: 46.8%, Trichodina spp. on the skin: 25.5%) accounted for the highest proportion (41.3%) of diseases, followed by hemorrhagic disease by Aeromonas hydrophila infection (20.5%), disease with white nodules in internal organs by Edwardsiella ictaluri infection (15.8%) disease, pale gills and liver (5.4%) and jaundice (0.5%). The proportion of the hemorrhagic disease increased in the higher temperature season, whereas the white nodule disease was more common at low temperatures (about 27-29C), when the water resource comes from the upper stream, creating high COD concentration. Besides, ectoparasitic infections occurred all year round in the catfish ponds, especially in the rainy season combined with adverse environmental parameters of the pond. The results suggest that precautionary measures should be taken at the major hotspots of disease, during the onset of the disease.