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In this study, we investigated the effects of the SARS\u2010CoV\u20102 spike protein S1 stimulation on neuroinflammation in BV-2 microglia. Analyses of culture supernatants revealed an increase in the production of TNF-\u03b1, IL-6, IL-1\u03b2 and iNOS\/NO. S1 also increased protein levels of phospho-p65 and phospho-I\u03baB\u03b1, as well as enhanced DNA binding and transcriptional activity of NF-\u03baB. These effects of the protein were blocked in the presence of BAY11-7082 (1\u00a0\u00b5M). Exposure of S1 to BV-2 microglia also increased the protein levels of NLRP3 inflammasome and enhanced caspase-1 activity. Increased protein levels of p38 MAPK was observed in BV-2 microglia stimulated with the spike protein S1 (100\u00a0ng\/ml), an action that was reduced in the presence of SKF 86,002 (1\u00a0\u00b5M). Results of immunofluorescence microscopy showed an increase in TLR4 protein expression in S1-stimulated BV-2 microglia. Furthermore, pharmacological inhibition with TAK 242 (1\u00a0\u00b5M) and transfection with TLR4 small interfering RNA resulted in significant reduction in TNF-\u03b1 and IL-6 production in S1-stimulated BV-2 microglia. These results have provided the first evidence demonstrating S1-induced neuroinflammation in BV-2 microglia. We propose that induction of neuroinflammation by this protein in the microglia is mediated through activation of NF-\u03baB and p38 MAPK, possibly as a result of TLR4 activation. 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