Virulent Aeromonas hydrophila (vAh) has attributed nearly $35 million dollars in economic losses within the US farm-raised catfish industry. This bacterial pathogen infects both channel and hybrid catfish causing internal and external hemorrhaging, exophthalmia and death. During an outbreak, farmers can lose over 50% of a harvest yield in less than a week, thereby increasing the urgency for more effective preventative measures. One affordable and efficacious candidate for vAh control involves the utilization of a bacterin vaccine, which is comprised of killed vAh bacteria. This approach should elicit a robust immune response while minimizing regulatory hurdles associated with other vaccine preparations such as live attenuated or modified vaccine preparations. Recently, our research team formulated and tested an oral bacterin vaccine against various vAh strains with and without the inclusion of an adjuvant. At 3 and 12 weeks, the bacterin vaccines showed protection against a Mississippi and Alabama vAh isolate and cross protection was demonstrated. Antibody presence was proposed as a potential mechanism of protection; thus the aim of the present study was to assess whether immune serum could provide protection against vAh. To evaluate the ability of immune serum to provide protection, we used 3 vAh strains (ALG-15-097, S14-452, ML09-119) to generate serum following parenteral immunization with formalin killed bacterins. Briefly, channel catfish (~20g) were IP injected and boosted at 9 weeks with formalin killed vAh strains. Fish were bled and immune serum was collected at 9 and 12 weeks post injection. Following collection of the anti-vAh serum, we conducted passive immunization in (~10 g) channel catfish with the following groups: control sera, heat-inactivated control sera, vAh immune sera, and heat-inactivated vAh immune sera. Three trials were conducted. For trials 1 and 2, fish were injected with 100mL of antisera and heat-inactivated antisera (T1: S14-452; T2: ML09-119) and were exposed with the corresponding vAh strain 24 h post-injection. The final trial evaluated cross-protection potential with the following groups: heat-inactivated S14-452 anti-serum, heat inactivated ML09-119 anti-sera, & control sera, and naive S14-452, ML09-119, & control sera then were immersion challenged using the fin clip model to ALG-15-097 (1.59 x 107 CFU/mL) 24 h post-injection. In all three trials, 100% protection was observed in all groups injected with anti-vAh or heat-inactivated anti-vAh sera suggesting immune serum provided protection against homologous and heterologous isolates of virulent A. hydrophila in channel catfish fingerlings. Results of this study help define the role of immune serum in providing protection against vAh.