Brain injury in extremely premature infants (gestational age <32 weeks) causes lifelong neurological sequelae, but the differentially expressed plasma proteins remains unclear. Nineteen extremely premature infants were enrolled, including 10 with brain injury and 9 without brain injury. Plasma proteomic sequencing were performed. Differential proteins were identified using t test analysis, followed by enrichment analyses. univariate logistic regression and LASSO were applied to identify informative clinical variables. Forty-four differential proteins were identified, which were mainly enriched in cytoskeleton-related functions. Four hub characteristic proteins were screened, including phosphoglycerate kinase 2 (PGK2), metallothionein, C-myc promoter-binding protein (MYCPP), and peroxisomal trans-2-enoyl-CoA reductase (PECR).