Aldehyde dehydrogenases (ALDHs) belong to a super-family of detoxifying proteins and perform a significant role in developing epithelial homeostasis, protecting cells from toxic aldehydes and drug resistance. However, the activity and function of these detoxifying proteins remain unknown, especially in fish. In our research, we aimed to study functions of aldehyde dehydrogenase 7A1 (ALDH7A1) in Atlantic salmon infected by Aeromonas salmonicida. Recombinant ALDH7A1 (rALDH7A1) was verified by SDS-PAGE and western blot. The molecular mass of the deduced amino acid sequence of rALDH7A1 is 58.9 kDa with an estimated pI of 7.09. Only a low complexity region (141yvegvgevqeyvdv153) without a signal peptide existed in rALDH7A1. Results of ELISA indicated that rALDH7A1 exhibited apparent binding activities with A. salmonicida and its expression was highest in fish kidney. A Real-Time PCR (qRT-PCR) assay in kidneys confirmed that fish in this experiment were authentically infected and bacterial loads in rALDH7A1-adminsitered fish were significantly reduced at an early stage of infection. Meanwhile, we found the mRNA expression of NF-kβ, P-38 MAPK, caspase-3 and TNF-α were mainly up-regulated at 72 h in the kidneys and livers of highly infected fish injected with rALDH7A1, and the same variation trend existed in fish spleens at 12 h. Consistent with these observations, neutralization experiments in vivo indicated that rALDH7A1 could obviously reduce the death rate compared to the BSA and control group. Taken together, we concluded that rALDH7A1 could act in host immune defense against bacterial infection and decrease the mortality rate of Atlantic salmon at early stages of infection with A. salmonicida.