A novel pathogenic Gram-negative, the rod-shaped bacterium was isolated from Lutjanus ehrenbergii, Lethrinus borbonicus, Rhabdosargus haffara and Scarus ghobban marine fishes of the Red Sea at Hurghada, Egypt. A total number of 25 out of 180 (13.9%) fishes were clinically diseased and exhibited a series of clinical signs, including skin darkness, hemorrhages especially at the base of fins, exophthalmia, skin ulcers, fin rot, swollen intestine and congestion or paleness of the internal organs. The morphological and biochemical characteristics of the 25 isolates were homogenous and were identified as Pseudomonas abyssi. Phylogenetic analysis of the 16S rRNA gene sequence showed that the isolated strains were closely related to the members of the genus Pseudomonas and shared the highest sequence identities (100%) with P. abyssi MT5 (GenBank accession no. MF962536.1)(100%). Thus, based on 100% identity with P. abyssi MT5 from GenBank, this isolate was P. abyssi. In the experimental study, it was pathogenic to Rhabdosargus haffara and sensitive to chloramphenicol, tetracycline, ciprofloxacin, ofloxacin, tobramycin, clindamycin, gentamycin and amoxicillin/clavulanic acid. Furthermore, AgNPs strongly inhibited P. abyssi growth and recorded a minimum inhibitory concentration (MIC) of 8 µg/mL. Blood vessels congestion, degenerative and necrotic lesions were detected in histopathological sections of the hepatopancreatic, splenic and posterior kidney tissues of Rhabdosargus haffara experimentally infected with P. abyssi.