Abstract:[Background] Forest musk deer are valuable economic animals in China. Captive musk deer populations frequently suffer from bacterial diseases, and thus studying the related pathogens is of great significance for the prevention and control of diseases attacking forest musk deer. [Objective] To investigate the drug resistance and pathogenicity of the microorganisms causing the death of a forest musk deer. [Methods] Bacteria were isolated from a deceased musk deer and identified. The drug susceptibility, pathogenicity in mice, and resistance gene and virulence genes of the isolates were studied. [Results] The forest musk deer suffered from mixed infection of Staphylococcus lentus (named 23HYSL) and Escherichia coli (named strain 23HYEC). The strain 23HYSL was resistant to aztreonam, lincomycin, tetracycline, and sulfisoxazole, while strain 23HYEC was a multi-drug resistant E. coli strain producing extended-spectrum β-lactamases. The median lethal doses (LD50) of strain 23HYSL and strain 23HYEC in mice were 1.39×108 CFU and 8.97×107 CFU, respectively. The pathological sections showed that the mixed infection caused severer spleen lesions and facilitated the colonization of strain 23HYEC in the heart and liver of mice. Both strains carried the resistance genes sul2, tetA, tetC, blaTEM, and blaCTX-M. In addition, strain 23HYSL carried the virulence gene clfa, while strain 23HYEC carried 5 virulence genes including astA. [Conclusion] We isolated S. lentus from forest musk deer for the first time and studied the drug resistance and pathogenicity of this bacterium in the case of mixed infection with astA+ E. coli, giving insights into the prevention of related diseases and the rational use of drugs.