Red Dead Syndrome (RDS) in cultured white leg shrimp (Litopenaeus vannamel) has been occurring in many shrimp cultured farms in some provinces of Central-South provinces, Vietnam for the last some years. In 2010, molecular biology techniques (PCR and RT-PCR), histopathology, bacteriology and transmission electron microscopy (TEM) were used in analysis of 30 disease shrimp specimens and 14 healthy shrimp specimen's (25-30 shrimps per specimen) in order to detect the causative agent of the above mentioned disease. The research results showed that white spot syndrome virus (WSSV) infected in disease shrimp group (with 90 percent infection rate). None of specimen was infected with Taura syndrome virus (TSV). Both groups of disease and healthy shrimps were infected with some bacterial species at low infection rate (30 percent). For detecting the main causative agent of the disease, an infectious experiment was carried out. Filtered virus suspension (0.2 um filter, from disease shrimps), bacterial suspensions from each bacterial strain (Staphylococcus sp1, Vibrio alginolyticus or Vibrio vulnificus) and a mixture of virus and bacterial suspensions (1:1) were injected into healthy shrimps. The experimental results proved that WSSV was the main causative agent causing Red Dead Syndrome in cultured white leg shrimp.