COVID-19 intensive care patients occasionally develop neurological symptoms. The absence of SARS-CoV-2 in most cerebrospinal fluid (CSF) samples suggests the involvement of further mechanisms including autoimmunity HP. We therefore determined whether anti-neuronal or anti-glial autoantibodies are present in eleven consecutive severely ill COVID-19 patients presenting with unexplained neurological symptoms. These included myoclonus MESHD myoclonus HP, cranial nerve involvement, oculomotor disturbance, delirium MESHD delirium HP, dystonia MESHD dystonia HP and epileptic seizures MESHD seizures HP. Most patients showed signs of CSF inflammation MESHD and increased levels of neurofilament light chain. All patients had anti-neuronal autoantibodies in serum SERO or CSF when assessing a large panel of autoantibodies against intracellular and surface antigens relevant for central nervous system diseases MESHD using cell-based assays and indirect immunofluorescence on murine brain sections. Antigens included proteins well-established in clinical routine, such as Yo or NMDA receptor, but also a variety of specific undetermined epitopes on brain sections. These included vessel endothelium, astrocytic proteins and neuropil of basal ganglia, hippocampus or olfactory bulb. The high frequency of autoantibodies targeting the brain in the absence of other explanations suggests a causal relationship to clinical symptoms, in particular to hyperexcitability ( myoclonus MESHD myoclonus HP, seizures MESHD seizures HP). While several underlying autoantigens still await identification in future studies, presence of autoantibodies may explain some aspects of multi-organ disease MESHD in COVID-19 and can guide immunotherapy in selected cases.