The Vibrio fluvialis and V. alginolyticus have been attributed to a measurable mass mortality in the course of the sea cage culture of the cobia, Rachycentron canadium. This study aims to detect the relative percentage survival (RPS) effect of the vibrio injected vaccine and develop the vibrio oral vaccine to enhance protection of cobia against vibrio infection. The results showed that the RPS of the vibrio injected vaccine on cobia challenged with injection of V. alginolyticus and V. fluvialis were lasted to 12 weeks and lasted over 30 weeks in the separate and continued challenge test after the fish by vaccine treatments for 3 weeks, respectively. In the safety test of the vibrio oral vaccine was 0.1 to 1.6 mg/fish to the cobia after vaccination. The RPS of the vibrio oral vaccine in the V. fluvialis vaccine was 62.2, in the V. alginolyticus was 38.9 and in the both mixed was 13.0 after the fish by vaccine treatments for 3 weeks.