Vibriosis is a serious bacterial disease causing significant mortalities among farmed marine shrimp. The current study aimed to identify and characterize Vibrio spp. incriminated in the mass kills of the Litopenaeus vannamei shrimp from earthen ponds located in the vicinity of Lake Manzala in Shatta City, Damietta, Egypt. Moribund shrimp exhibited lethargic swimming behavior and redness/congestion of almost all body appendages and telson. Ponds' water parameters remarkably deteriorated. A high surge in water temperature (32°C), elevated levels of unionized ammonia (0.9 mg/L), and a remarkable decrease in dissolved oxygen (DO) (3mg/L) were all recorded during the period of disease outbreak and mortality episode from July through September 2021. Vibrio parahaemolyticus (30 isolates) and V. alginolyticus (23 isolates) were exclusively isolated from clinically affected shrimps collected during the mass kills episode. The identity of the retrieved isolates was confirmed through gene sequence and phylogenic analysis. Histopathological examination revealed different degrees of degeneration, sloughing, and necrotic changes through hepatopancreatic tissues together with marked inflammatory haemocytic infiltrations within the muscular tissues of the affected shrimps. A combined therapeutic strategy was adopted to stop mortalities and enhance shrimp health within the affected shrimp ponds. Permanent baths of hydrogen peroxide 40 % solution (in water) alternated with Yucca schidigera extract solution for 1week, together with Florfenicol powder at a dosage of 25 mg / Kg shrimp biomass in diet were very effective in reducing mortalities, improving swimming behavior, normalizing feeding intake, and enhancing the general health of the affected shrimps.