Objective To assess the role of multiple serological markers in the prediction of post-stroke cognitive impairment （PSCI） in elderly patients with acute ischemic stroke （AIS）. Methods A total of 326 patients with AIS treated in the Department of Neurology of the First Affiliated Hospital of Harbin Medical University from January 2019 to January 2023 were retrospectively enrolled. According to the Mini Mental State Scale （MMSE） score at 6 months after onset， patients were divided into PSCI group （MMSE score ≤ 26 points） and non PSCI group （MMSE score ＞ 26 points）. General information and serological indicators were compared between the two groups. Risk factors for PSCI were screened using multifactorial Logistic regression. The efficacy of serological markers in predicting PSCI was rated using receiver operating characteristic （ROC） area under curve （AUC）. Results Among 326 patients， 127 （38.96%） experienced PSCI 6 months after onset. The proportion of patients with age ＞ 75， diabetes and stroke history， NIHSS score， homocysteine， uric acid， neutrophil/lymphocyte ratio （NLR）， low-density lipoprotein cholesterol （LDL-C）， C-reactive protein （CRP） at admission of PSCI group were significantly higher than those of non PSCI group （P＜ 0.05）； The high-density lipoprotein cholesterol （HDL-C） of PSCI group was lower than that of non PSCI group， and the difference was statistically significant （P ＜ 0.05）. The results of multifactorial logistic regression analysis showed that age ＞ 75 years （OR=1.422， 95%CI：1.050-1.926， P=0.023）， high NIHSS score at admission （OR=1.791， 95%CI：1.324-2.423，P ＜ 0.001）， high CRP （OR=1.305， 95%CI：1.077-1.581， P=0.007）， high NLR （OR=1.520， 95%CI： 1.196-1.933， P ＜ 0.001）， and high LDL-C （OR=1.387， 95%CI：1.132-1.699， P=0.002） were all the independent risk factors for the development of PSCI in elderly patients with AIS. The ROC curve analysis results showed that the AUC of CRP， NLR， and LDL-C predicting PSCI in elderly AIS patients were 0.655 （95%CI： 0.595-0.715）， 0.813 （95%CI： 0.766-0.859）， and 0.735 （95%CI： 0.680-0.789）， respectively. Conclusions CRP， NLR and LDL-C are independent risk factors for the occurrence of PSCI in elderly patients with AIS， and they have a certain predictive ability for PSCI， with NLR having the highest predictive performance.