Mild cognitive impairment (MCI) is characterized by an abnormal decline in mental and cognitive function compared with normal cognitive aging. It is an underlying condition of Alzheimer’s disease (AD), an irreversible neurodegenerative disease. In recent years, neuroinflammation has been investigated as a new leading target that contributes to MCI progression into AD. Understanding the mechanism underlying inflammatory processes involved in the early onset of the disease could help find a safe and effective way to diagnose and treat patients. In this article, we assessed over twenty different blood and cerebrospinal fluid (CSF) inflammatory biomarker concentrations with immunoassay methods in patients with MCI (mild cognitive impairment), non-impaired control (NIC), and serum healthy control (HC). We performed group comparisons and analyzed in-group correlations between the biomarkers. We included 107 participants (mean age: 64.7 ± 7.8, women: 58.9%). CSF osteopontin and YKL-40 were significantly increased in the MCI group, whereas serum C-reactive protein and interleukin-6 were significantly higher (p< 0.001) in the NIC group compared with the MCI and HC groups. Stronger correlations between interleukin-1β and inflammasome markers were observed in the serum of the MCI group. We confirmed specific inflammatory activation in the central nervous system and interleukin-1β pathway upregulation in the serum of the MCI cohort.