The physico-chemical status of shrimp Penaeus monodon cultured at semi-intensive ponds in the coastal area of Thanjavur District, Tamil Nadu, India were investigated. The outbreak diseases were observed in the semi-intensive P. monodon culture ponds located at Adirampattinam, Rajamadam, Manora and Sedhubhavasatram during the study period from August 2008 to July 2010. The water quality parameters like turbitity, calcium, phosphate, silicate and ammonia levels were found to behighest ranges in the disease out break ponds than normal ponds. Where as, the dissolved oxygen, carbon-di-oxide and nitrate levels were slightly reduced from the optimal level in the disease out breaked ponds than normal ponds. The pathogenic bacteria and fungi were isolated and identified from the infected gills, intestine, and muscles shrimps. Totally 13 bacterial species and 21 fungal species were isolated from the infected shrimp samples. Among them, Enterococcus bacteria and Aspergillus group of fungus were the dominant microbes. The pathogenic bacteria and fungi were tested againt antibiotics susceptibility disc for their control. The antibiotic substances like Ampicillin exhibited highest antibacterial activity and Nystatin showed highest antifungal activity.