Colibacillosis, caused by avian pathogenic Escherichia coli (APEC) is a major problem for the poultry industry resulting in significant losses annually. Previous work in our lab and by others has shown that the increased serum survival gene (iss) is a common trait associated with the virulence of APEC. This gene was first described for its contributions to E. coli serum resistance. However, recently published research has called the contribution of iss to this trait into question. In the present study, the level of serum resistance conferred on an E. coli isolate by iss is examined. Additionally, the contribution of λ bor gene to E. coli serum resistance is studied, as iss is thought to be derived from bor and bor occurs commonly among E. coli. To better understand the iss and bor contributions to serum resistance, a series of iss and bor mutants was generated. An iss deletion (iss⁻) mutant showed a significant drop in its resistance to serum. Similarly, a bor mutant showed a drop in serum resistance but not as drastic as that observed with the iss mutant, suggesting that iss contributes more to serum resistance than bor in this E. coli strain. Also, when iss was reintroduced into the iss⁻ mutant the wild-type level of serum resistance was restored, confirming that the deletion of iss was responsible for the change in resistance seen in the mutant.