Abstract: Background and Objective: One of the problems which concern the cultivation of vannamei shrimps is the attack of vibriosis diseases caused by Vibrio harveyi bacteria. This study was aimed to examine the antibacterial potential of guava leaf extract (against V. harveyi bacteria to determine the effectiveness of guava leaf extract for the prevention of diseases. Materials and Methods: Treatments included administration of guava leaf extract mixed into feed at different dosages level and without administration of guava leaf extract (control). The control treatment consists of positive control (K+) and negative control (K-). After 14 days of trial period, all shrimp were challenged with V. harveyi RfR concentration of 106 CFU mL–1 except negative controls. Results: The results showed that administration of guava leaf extract at a dose of 5250 ppm (treatment C) was more able to suppress the growth of V. harveyi RfR bacteria on the 18th day which was 3.72 log CFU g–1 and decreased on the 21st day that is equal to 2.90 log CFU g–1. The highest total hemocyte count (THC) was found in the treatment of 5250 ppm (treatment C) i.e., on the 14th day, the 18th day and on 21st day while the percentage of hyaline cells after giving guava leaf extract for 14 days has increased, then decreased on the 18th day then increased again on the 21st day. While the percentage of granular/semigranular cells has decreased on the 14th day then increased again on the 18th and 21st days. Conclusion: Administration of guava leaf extract in feed could improve physiological status and to increase the relative survival of vaname shrimp when facing an infection of vibriosis.