Human herpesviruses (HHVs) can establish latency and be reactivated, also are neurotropic viruses that can trigger neurological disorders. HHV-6 is a herpesvirus that is associated with neurological disorders. Studies have reported the detection of HHV-6 in patients with COVID-19 and neurological manifestations. However, specific diagnoses of the neurological disorders caused by these viruses tend to be invasive or difficult to interpret. This study aimed to establish a relationship between miRNA and neurological manifestations in patients co-infected with COVID-19 and HHV-6 and evaluate miRNAs as potential biomarkers. Serum samples from COVID-19 patients in the three cohorts were analyzed. miRNA analysis by real-time polymerase chain reaction (qPCR) revealed miRNAs associated with neuroinflammation were highly expressed in patients with neurological disorders and HHV-6 detection. When compared with the group of patients without detection of HHVs DNA and without neurological alterations, the group with detection of HHV-6 DNA and neurological alteration, displayed significant differences in the expression of mir-21, mir-146a, miR-155 and miR-let-7b (p< 0.01). Our results reinforce the involvement of miRNAs in neurological disorders and provide insights into their use as biomarkers for neurological disorders triggered by HHV-6. Furthermore, understanding the expression of miRNAs may contribute to therapeutic strategies.