Introduction: There is growing evidence suggesting an association between Neurodegeneration and Inflammation playing a role in the pathogenesis of age-associated diseases, including Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI). A systematic review and meta-analysis were performed to verify evidence on the diagnostic accuracy parameters of the inflammatory cytokines Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Tumor Necrosis Factor (TNF-α). Method: A search of Medline, Scielo, Web of Science and Science Direct databases was performed and 9 observational studies associated with peripheral inflammatory biomarkers in CCL were identified. Mean (± SD) concentrations of these biomarkers and values of true positives (VP), true negatives (VN), false positives (FP) and false negatives (FN) for CCL and healthy controls (CS) were extracted from these studies. Result: Significantly higher levels of IL-10 were observed in subjects in the MCI group and Mini Mental State Examination (MMSE) scores were lower compared to CS. For the other investigations, no differences were found between the groups. Our meta-analysis for the TNF-α biomarker revealed high heterogeneity between studies in terms of sensitivity and specificity. Limitations: Lack of essential data in observational studies, which directly impacted the number of included studies. Conclusion: These findings do not support the involvement of inflammatory biomarkers for detection of MCI, although significant heterogeneity was observed. More studies are needed to evaluate the role of these cytokines in MCI, as well as in other stages of cognitive decline and all-cause dementias.