Background: Previous studies have suggested a correlation between alterations in the routine blood check markers and cognitive impairment. Objective: We aimed to explore the relationship between routine blood parameters and cognitive impairment. Methods: In this retrospective case-control study, 8,025 people over 60 years of age were enrolled from 51 community health centers in Luohu District of Shenzhen City from 2017 to 2018. According to the mini-mental state examination (MMSE) score and educational level, participants were divided into a cognitive impairment group (n=385) and normal cognitive function group (n=7,640). Nonparametric test, chi-square test, and binary logistic regression were applied to analyze the data. Results: Compared to the normal cognitive function group, the lymphocyte-to-monocyte ratio (LMR), packed-cell volume (PCV), and platelet count (PLT) in the cognitive impairment group were significantly lower (7.26 [5.50,8.81] vs. 7.45 [5.80,9.35]; 40.1 [36.65,42.95] vs. 40.5 [37.7,43.1]; 216 [190,258] vs. 228 [196,261], p<0.05, respectively), while the monocyte count and mean corpuscular hemoglobin concentration (MCHC) were higher (0.31 [0.25, 0.38] vs. 0.3 [0.24, 0.37]; 336 [330, 343] vs. 335 [328, 342], p<0.05, respectively). Additionally, MCHC [odds ratio (OR):1.011, 95% confidence interval (CI) :1.001–1.021, p = 0.033] and PCV [OR: 0.993, 95% CI: 0.987–0.999, p = 0.033) were independently associated with cognitive impairment. Conclusion: The alterations in some routine blood check parameters, including reduced LMR, PCV, and PLT, and elevated monocyte count and MCHC, may be associated with cognitive impairment.