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<i>Edwardsiella ictaluri</i> and <i>Flavobacterium covae</i> are pervasive bacterial pathogens associated with significant losses in catfish aquaculture. Bacterial coinfections have the potential to increase outbreak severity and can worsen on-farm mortality. A preliminary assessment of in vivo bacterial coinfection with <i>E. ictaluri</i> (S97-773) and <i>F. covae</i> (ALG-00-530) was conducted using juvenile channel catfish (<i>Ictalurus punctatus</i>). Catfish were divided into five treatment groups: (1) mock control; (2) <i>E. ictaluri</i> full dose (immersion; 5.4 × 10⁵ CFU mL⁻¹); (3) <i>F. covae</i> full dose (immersion; 3.6 × 10⁶ CFU mL⁻¹); (4) <i>E. ictaluri</i> half dose (immersion; 2.7 × 10⁵ CFU mL⁻¹) followed by half dose <i>F. covae</i> (immersion; 1.8 × 10⁶ CFU mL⁻¹); and (5) <i>F. covae</i> half dose followed by half dose <i>E. ictaluri</i>. In the coinfection challenges, the second inoculum was delivered 48 h after the initial exposure. At 21 days post-challenge (DPC), the single dose <i>E. ictaluri</i> infection yielded a cumulative percent mortality (CPM) of 90.0 ± 4.1%, compared with 13.3 ± 5.9% in the <i>F. covae</i> group. Mortality patterns in coinfection challenges mimicked the single dose <i>E. ictaluri</i> challenge, with CPM of 93.3 ± 5.4% for fish initially challenged with <i>E. ictaluri</i> followed by <i>F. covae</i>, and 93.3 ± 2.7% for fish exposed to <i>F. covae</i> and subsequently challenged with <i>E. ictaluri</i>. Despite similarities in the final CPM within the coinfection groups, the onset of peak mortality was delayed in fish exposed to <i>F. covae</i> first but was congruent with mortality trends in the <i>E. ictaluri</i> challenge. Catfish exposed to <i>E. ictaluri</i> in both the single and coinfected treatments displayed increased serum lysozyme activity at 4-DPC (<i>p</i> < 0.001). Three pro-inflammatory cytokines (<i>il8</i>, <i>tnfα</i>, <i>il1β</i>) were evaluated for gene expression, revealing an increase in expression at 7-DPC in all <i>E. ictaluri</i> exposed treatments (<i>p</i> < 0.05). These data enhance our understanding of the dynamics of <i>E. ictaluri</i> and <i>F. covae</i> coinfections in US farm-raised catfish.