Background: We evaluated the levels of the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and caspase-3 in the cerebrospinal fluid (CSF) and serum of COVID-19 patients to improve our knowledge about underlying mechanisms caused by this virus in central nervous system involvement., Case Presentation: This case series study included six COVID-19 patients from March 26, 2020, to April 17, 2020, and six healthy control patients. CSF and serum levels of TNF-α, IL-1β, and caspase-3 have been assayed using monoclonal antibodies-based ELISAs.Patients with COVID-19 had significantly higher level of IL-1β, TNF-α, and caspase-3 in serum (239.16±35.73 pg/ml, 100.50±12.49 pg/ml, 3.58±0.11pg/ml, p < 0.001) and CSF (146.66±17.55 pg/ml, 63.16±14.68 pg/ml,3.22±0.03pg/ml, p<0.001), respectively as compared to control. In addition, our results showed that these biomarkers were significantly higher in serum compared with CSF of the COVID-19 patients (p<0.001)., Conclusion: This study provides essential information for understanding the pathogenesis of COVID-19 infection and sheds light on the potential mechanisms of virus transmission. The obtained data could be useful for designing new prevention and treatment strategies for COVID-19., Competing Interests: None of the authors has any conflict of interest to disclose.