Background: Neonates are highly susceptible to infection given their immature immune system. Previous studies on proteins related to neonatal infection mainly focused on maternally acquired antibodies, but without comprehensive studies on multiple immune-response-related proteins associated with neonatal infection. Methods: We conducted a nested case-control study within the SZBBTwin cohort, measuring 92 immune-response-related proteins in cord plasma of 149 twins (including 34 discordant twin pairs) with Olink Proteomics. All twins were followed for diagnoses of infection from birth until 27 days of age. Wilcoxon rank-sum test was used to determine differentially expressed proteins (DEPs), the predictive performance of which was evaluated by ROC curve, and their functions and pathways were annotated through enrichment analysis. Logistic regression was used to assess the associations between level of proteins and risk of neonatal infection. Results: Five DEPs (ITGA11, FCRL6, DDX58, SH2D1A, and EDAR) were identified for neonatal infection. The AUC achieved 0.835 for the five DEPs, which were mainly enriched in the NF-κB pathway. A higher level of ITGA11 was associated with an increased risk of neonatal infection in both the analyses of all twins and discordant twin pairs. Conclusions: Multiple immune-response-related proteins in cord plasma, particularly ITGA11, are associated with the risk of neonatal infection in twins.