Abstract: To investigate the etiology and prevention strategies for the emerging disease “white body disease” (provisionally named) in Macrobrachium rosenbergii, epidemiological studies were conducted to identify the typical symptoms and potential pathogens of the disease, followed by developing therapeutic approaches. The results showed that the disease mainly prevailed in M. rosenbergii broodstock farms. Clinical symptoms in affected prawns encompass abdominal muscles opacity and hepatopancreas atrophy, with histopathological characteristics include muscle tissue rupture, necrosis and sloughing of hepatopancreatic epithelial and intestinal mucosal layer cells, coupled with an augmented presence of inflammatory cells in the gills. Challenge experiments using hepatopancreas tissue fluid from diseased prawn confirmed the presence of pathogenic bacteria. Eight dominant strains isolated from infected hepatopancreas were provisionally identified as Citrobacter portucalensis and Klebsiella aerogenes. Artificial infection experiments indicated that all isolated strains were pathogenic to M. rosenbergii, with C. portucalensis XN241202 and K. aerogenes GY241001 exhibiting the highest pathogenicity. Based on these findings, the disease was tentatively named White Syndrome (WS). In vitro antibacterial tests showed that antibiotics such as cefoperazone, enrofloxacin, levofloxacin, and florfenicol, along with plant-derived drugs including thymol, oregano oil, chelerythrine, and Agastache rugosa extracts, exerted significant inhibitory effects on strains XN241202 and GY241001. In vivo experiments showed that dietary supplementation with 1 mg/kg of enrofloxacin, florfenicol, or oregano oil significantly reduced the mortality rate of WS prawns (P<0.05). These findings provide an important scientific basis for the effective control of WS and are critical for safeguarding M. rosenbergii breeding security.