Objective To investigate the correlation between the expression levels of intercellular adhesion molecule-1 (ICAM-1), soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in serum of patients with acute cerebral infarction (ACI) and their prognosis, and to analyze their predictive value for poor prognosis. Methods A retrospective study was conducted on 104 ACI patients who were diagnosed and treated in Zhengzhou Yihe Hospital from May 2021 to May 2023. After treatment, the prognosis was evaluated based on the modified Rankin Scale (mRS) at 90 days, and the patients were divided into a poor prognosis group (n=38) and a good prognosis group (n=66). The serum levels of ICAM-1, sLOX-1, and Lp-PLA2 were compared between the two groups. The influencing factors of prognosis were analyzed by multivariate Logistic regression. To evaluate the predictive value of serum ICAM-1, sLOX-1 and Lp-PLA2 in poor prognosis 1 month after treatment. Results The levels of serum ICAM-1, sLOX-1, and Lp-PLA2 in the poor prognosis group were higher than those in the good prognosis group 1 month after treatment (P<0.05). NIHSS score, neuron-specific enolase (NSE), central nervous specific protein (S100-β) and ICAM-1, sLOX-1 and Lp-PLA2 levels one month after treatment were independent risk factors for poor prognosis (P<0.05). The AUC of ICAM-1, sLOX-1 and Lp-PLA2 combined predicted poor prognosis at 1 month after treatment was greater than that of single index and any two indexes combined (P<0.05). Conclusion The levels of serum ICAM-1, sLOX-1, and Lp-PLA2 in ACI patients are independent risk factors for poor prognosis, and combined detection of their levels has certain predictive value for prognosis.