Sinus venous thrombosis has been linked to immunization with the ChAdOx1 nCov-19 vaccine. The initial trigger for this serious adverse event has not been determined. We analyzed the ChAdOx1 nCov-19 vaccine by biochemical and proteomic methods. We found that the vaccine, in addition to the adenovirus vector, contains substantial amounts of both human and non-structural viral proteins. Among the human proteins, heat-shock proteins and cytoskeletal proteins were particularly abundant. The often-observed strong clinical reaction one or two days after vaccination is likely associated with the detected protein impurities. A linkage to later immune-related adverse events is also conceivable. The here reported identification of specific classes of protein impurities should guide and accelerate efforts to increase the purity of the vaccine and increase its safety and efficacy.