This study aimed to evaluate the growth, survival rate, and resistance to acute hepatopancreatic necrosis disease (AHPND) of white leg shrimp (Penaeus vannamei) by using Lactobacillus plantarum, Lactobacillus fermentum, and Pediococcus pentosaceus mixed with feed, and at the same time supplying CNP in a ratio of 15:1:0.1 to the water. As a result, the treatments that shrimp were fed with feed containing lactic acid bacteria (LAB), especially L. plantarum, have increased shrimp growth, total hemocyte cells, granulocyte cells, and hyaline cells significantly (p < 0.05) in comparison to the control group. The supply of CNP to the water has promoted the intensity of V. parahaemolyticus effects on shrimp health and significantly decreased total hemocyte cells, granulocyte cells, and hyaline cells by 30–50% in the period after three days of the challenge, except in L. plantarum treatment, which had only a 20% decrease compared to other treatments. In CNP supplying treatments, the AHPND infected rate and mortality of shrimp were higher than those in other treatments. In summary, the supply of CNP had significantly reduced the shrimp’s immune response and promoted
the susceptibility of shrimp to AHPND in both cases of use with and without LAB-containing diets.