Current interventions targeting antimicrobial resistance (AMR), a major impact on commercial pork production, focus on reducing the emergence of AMR by minimising antimicrobial usage through antimicrobial stewardship and a range of alternative control methods. Although these strategies require continued advancement, strategies that directly aim to reduce or eliminate existing antimicrobial resistant bacteria, specifically bacteria resistant to critically important antimicrobials (CIAs), need to be investigated and established. This study established an in vivo model for examining the effects of postbiotics, in the form of Lactobacillus acidophilus fermentation products (LFP) and Saccharomyces cerevisiae fermentation products (SFP), on the shedding of extended-spectrum cephalosporin (ESC)-resistant E. coli. The model was successful in demonstrating the presence of ESC-resistant E. coli as evidenced by its detection in 62 of 64 pigs. There was a strong trend (p = 0.065) for the SFP postbiotics to reduce the shedding of ESC-resistant E. coli, indicating positive impacts of this additive on reducing the carriage of bacteria resistant to CIAs. Overall, this in vivo model enables future evaluation of strategies targeting ESC-resistant E. coli while increasing our knowledge on the carriage of ESC-resistant E. coli in pigs.