AIM: To analyze the compliance rate and possible influencing factors for blood concentration of meropenem in patients with central nervous system (CNS) infections, and to provide basis for optimizing the administration of meropenem in the patients. METHODS: A retrospective analysis was performed in patients who were treated with meropenem and monitored the concentration (Cmin) from January 2021 to December 2022. The basic clinical data of the patients were recorded, and the achievement of meropenem blood concentration was counted. Univariate and binary logistic regression analysis were used to analyze the influencing factors for the e substandard steady-state blood trough concentration of meropenem. The ROC curve was drawn to predict the clinical characteristics. RESULTS: Forty-five cases were included. The median Cmin of meropenem was 4.14 (0.82, 16.29) mg/L, and 51.11% reached the target range with 4 mg/L. Binary logistic regression analysis showed that serum creatinine value and using mannitol were risk factors for the substandard steady-state blood trough concentration of meropenem (P<0.05). When serum creatinine value was less than 84 μmol/L, the area under the ROC curve was the largest (0.916), the sensitivity was 0.783, the specificity was 0.955, and the Youden index was 0.738. CONCLUSION: The Cmin compliance rate of meropenem blood concentration in patients with CNS infection is low, especially in patients with hyperfunction of kidney and those who using mannitol. It is necessary to conduct drug concentration monitoring to optimize the administration of meropenem in patients with CNS infection.