AbstractAeromonas septicemia still represents a serious challenge facing the global aquaculture sector. In the present study, Aeromonas caviae and A. veronii were isolated from four diseased European seabass (Dicentrarchus labrax) farms experiencing a high mortality rate. Diseased fish showed haemorrhages on the external body surface with exophthalmia, cataracts, scale desquamation, skin ulcers and fin erosions. The most common post‐mortem findings were congested internal organs, particularly the liver and posterior kidney. Twenty‐eight A. Veronii and 11 A. caviae isolates were identified biochemically by the Vitek 2 system and then confirmed by PCR and phylogenetic analysis. Hemolysin (hlyA) and aerolysin (aer) were the most abundant virulence genes in the recovered isolates, followed by cytotoxic enterotoxin (act) and heat‐stable enterotoxin (ast). A. caviae was more virulent than A. veronii for D. labrax fingerlings as LD50 ranging between (>1 × 108–6.2 × 107) for A. veronii and (2.9 × 107–8.3 × 107) for A. caviae. The sensitivity test indicated the effectiveness of norfloxacin, doxycycline and oxytetracycline against the tested isolates. Serum cortisol significantly increased in the infected groups, while catalase and glutathione peroxidase activities significantly decreased at 2 days post‐infection (DPI) and then increased at 6 DPI. The presence of virulence genes was associated with bacterial pathogenicity expressed in fish mortality rate. Virulence genes also drastically affect cortisol levels more than catalase and glutathione peroxidase levels.