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This study investigated a practical, inexpensive, and effective vibriosis control a serious cause of severe mortalities of cultured European sea bass (Dicentrarchus labrax) using FKC bacterins of Listonella anguillarum or Vibrio alginolyticus, their cross-protection against L. anguillarum or V. alginolyticus, and their most suitable administration route in D. labrax. The results of L. anguillarum or V. alginolyticus that naturally infected D. labrax during the summer season revealed mass mortalities, hemorrhagic ulceration on different body areas, eye opacity, and many internal pathological lesions. The two pathogens were identified by traditional methods and MALDI-TOF-MS. The gills were recorded with the highest incidence of the two bacteria. Experimental results indicated the superiority of V. alginolyticus FKC bacterin in protection against V. alginolyticus and cross-protection against L. anguillarum. Intraperitoneal injection recorded better immunization results than prolonged immersion for 2 h and dipped immersion for 1 min. In conclusion, intraperitoneal injection of V. alginolyticus FKC bacterin could induce protection against V. alginolyticus and cross-protection against L. anguillarum in D. labrax that could be a valuable means for vibriosis control.