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This study assessed the effect of poly-β-hydroxybutyrate (PHB) on the growth, survival, and disease resistance of Pacific white shrimp Litopenaeus vannamei. A 20-d feeding test using 30-d-postlarval Pacific white shrimp (100 shrimp/ tank) tested three different diets: 0.3 g PHB/kg diet, 0.5 g PHB/kg diet, and commercial feed containing no PHB as the control. The feeding test was followed by a 10-d bacterial challenge test using Vibrio harveyi. After the feeding test, the highest average final body weight, specific growth rate, and total biomass (mean ± SD = 0.44 ± 0.28 g, 28.82 ± 2.08%/d, and 25.91 ± 7.19 g, respectively) were found in the 0.5 g PHB/kg diet group, while the 0.3 g PHB/kg diet showed the highest survival rate (67.00 ± 8.83%). After the Vibrio harveyi challenge test, both PHB diet treatments resulted in the same significantly higher survival rate (96.66 ± 4.71%) compared with the control treatment (70.00 ± 4.71%). The highest body weight gain during the challenge test was seen in the 0.5 g PHB/kg diet group. Total abundance of heterotrophic bacteria and Vibrio spp. was relatively similar for all treatments. Histopathological analysis showed that hepatopancreas samples from PHB-supplemented Pacific white shrimp showed decreasing tubular epithelial cell lesions as a result of Vibrio harveyi infection, suggesting that PHB protected the hepatopancreas of Pacific white shrimp from the destructive effect of Vibrio harveyi infection. Supplementation at 0.5 g PHB/kg significantly increased Pacific white shrimp survival and growth with or without Vibrio harveyi infection and, thus, has high potential for further use in Pacific white shrimp aquaculture.