In this study, we aimed to investigate the relationship between salivary cortisol content and secondary mild cognitive impairment (MCI), thereby supporting the prediction of MCI in clinical practice. In this study, the salivary cortisol levels were examined in 120 patients with MCI after cerebral ischemic stroke (CIS) (CIS-MIC) and 80 CIS patients without MIC (CIS). The clinical data were compared among these patients with different cortisol levels. The salivary level of cortisol was significantly higher in patients with CIS-MIC (0.85-3.65 nmol/L) than that in those with CIS (0.52-1.21 nmol/L). The categorized analysis by CIS-MIC quartile showed that patient age, hyperlipidemia, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), etc. were significantly increased with increasing salivary cortisol levels. Moreover, univariate and multivariate logistic regression analyses revealed that the MCI risk of patients in the first quartile was 0.35 and 0.41 times, respectively, of the fourth quartile. Multiple linear regression showed that patient age, the time of rescue, and the salivary cortisol level were independent factors in the Mini-Mental State Exam (MMSE) score of MCI patients. Meanwhile, the receiver operating characteristic (ROC) curve showed that the area under the curve of salivary cortisol as a diagnostic marker for MCI after CIS was 0.982, with sensitivity of 0.973 and specificity of 0.980. In this study, we found that salivary cortisol level was an independent risk factor of MCI after CIS. A higher salivary cortisol level indicated a higher probability of MCI occurrence, and salivary cortisol level can be used as a predictive marker for MCI occurrence.