Pakistan has a big livestock population in all provinces. Cattle breeds infected by diseases according to their environment. Balochistan is the warmest region of Pakistan. We studied seroprevalence of Brucellosis, Hemorrhagic Septicemia (HS) and FMD in Tharparker and Bhagnari cattle breeds of Sindh and Balochistan province of Pakistan. Brucellosis is an infectious disease, mainly caused by Brucella abortus bacteria. Hemorrhagic Septicemia (HS) is a major bacterial disease of cattle and buffaloes, caused by Pasteurella multicoda. Foot and Mouth Disease is severe, highly contagious, viral disease. FMD affects cloven hoofed animals including cattle. Thirty five blood samples of Tharparker and Bhagnari cattle were collected from the Sindh and Balochistan province, respectively. These samples were diagnosed against Brucellosis, HS and FMD by using different serological tests. Brucellosis was diagnosed by RBP (Rose Bengal Plate) test and confirmed with ELISA test. Hemorrhagic Septicemia was diagnosed by indirect haemagglutination (IHA) technique. To diagnose FMD ELISA test was carried out. As a result, Brucellosis and HS was not found in all samples but 60 percent cattle were affected with FMD. It was recorded cattle were vaccinated against Brucellosis and HS. However, cattle were not vaccinated for FMD. So, It was concluded that Tharparker and Bhagnari cattle can be infected equally but on the basis of this study, Tharparker cattle sampled from different private farms was found more infected by with FMD because the Bhagnari cattle at Govt. Livestock farm was vaccinated routinely against FMD. This fact justifies that following study in the field of Brucellosis, HS and FMD identification will help to effectuate control measures. Regular disease surveillance was recommended to have a healthy cattle population.