Cobalt is an essential micronutrient but becomes toxic at elevated concentrations, requiring microorganisms to balance acquisition and detoxification. Aeromonas hydrophila, an opportunistic aquatic pathogen, is often encountered in metal-contaminated aquatic environments; however, its adaptive responses to cobalt stress have not been systematically characterized. Here, we applied quantitative proteomics to characterize the global protein response of A. hydrophila under cobalt stress. A total of