Herbal plants have gained enormous interest due to their immune, antioxidant, and antibacterial activities. The present study proposed that white poplar (Populus alba) leave extract (WPE) might provide a promising alternative to traditional antibiotics to treat Aeromonas veronii infection in Nile tilapia (Oreochromis niloticus). WPE showed an in vitro antibacterial activity [22±0.45mm inhibition zone, with minimum inhibitory concentration (MIC) and minimum bactericidal concen tration (MBC) of 60mg/mL] against A. veronii. For the in-vivo study, a factorial (2� 2) design was used to investigate the therapeutic effects of WPE on the antioxidant/immune status and blood biochemical parameters of Nile tilapia challenged with A. veronii. One-hundred sixty fish (33±1.5g) were assigned into four experimental groups, each with four replicates (4 glass tanks/group, 40 fish/group, 10 fish/tank) for 10days. In the first (1st) and 2nd groups, 0 and 1.5 mg/L WPE were applied in tank water, respectively, without fish being challenged. In the 3rd and 4th groups, 0 and 1.5mg/L WPE were applied in tank water, respectively, with fish intraperito neal inoculated with 0.2mL of A. veronii (0.5 �10 7 HIGHLIGHTS CFU). Aeromonas veronii infection significantly diminished the survivability, hepatic catalase, lysozyme activity, nitric oxide, immunoglobulin M, phagocytic %, total protein, albumin, and globulin. Moreover, a significant rise in the hepatic malondialdehyde, serum hepatorenal function indicators, cortisol, and glucose levels were conse quences of A. veronii challenge. Interestingly, the interaction between bacterial challenge and WPE application increased the survivability, antioxidant activity, and immune responses and reduced ALT levels of fish treated with WPE during the bacterial challenge. The serum creatinine, cortisol, and glucose levels were decreased in fish treated with WPE during the infection but still higher than in the non-infected fish either treated or not treated with WPE. In conclusion, WPE (1.5 mg/L) can be used as an antibacterial substance in fish farming to alleviate the detrimental impacts of A. veronii infection by enhancing the antioxidant/immune status of the infected fish. These outcomescould help reduce antibiotic usage in fish farms, which is conducive to the sustainable development of aquaculture.