Vibrio harveyi was used for challenge experiment in shrimp which were collected from indoor and outdoor experiments at the injection doses of 107 CFU/ml. Experimental shrimp were fed the food supplemented SPO oil with the rate of 0%, 0,1%, 0,2%, 0,4% for 30 days. A study was carried out to determine the histopathology of whiteleg shrimp (Penaeus vannamei) influenced by SPO oil and Vibrio harveyi. Histopathplogical observation revealed most of the challenged shrimp had lesions in skeletal muscle, including hemocytic infiltration and multifocal necrosis muscle. The foci of rod bacteria cells presented in the muscle of shrimp cultured outdoor. The hepatopancreas (HP) tubule epithelial cells separated and lose connection with tubule membrane. There are lack B, E and F cells in the HP tubules. Massive necrosis in HP tubules caused multufoci bacteria.