Background and aims Cases of cerebral venous sinus thrombosis (CVST) with concomitant thrombocytopenia were reported in young women following administration of COVID-19 Vaccine AstraZeneca (AZD1222/ChAdOx1-S). CVST is a rare but potentially fatal event, to be included in the differential diagnosis of headaches. Methods Case report of a previously healthy, 18-yr-old, female soldier who presented with NSAID-resistant frontal headache and remittent nausea in our casualty department 7 and 9 days after her first AZD1222-vaccination. No-smoker, no intake of oral contraceptives or other drugs reported. Results First visit, day 7 post vaccination: Neurol. examination and laboratory results were unremarkable, except for elevated D-dimers (4.12 mg/l [<.55]) and CRP (.6 mg/dL [<.5]). Platelets: 150 nl [150-450]. SARS-CoV-2-IgG: neg. Dual-energy CE-CCT/CTA revealed no CVST or other pathol. findings. The patient was discharged. Second visit, day 9 post vaccination: Persisting headache. No focal deficit, no petechiae. Thrombocytopenia (55 nl). D-dimers 15.29 mg/l, CRP 1.1 mg/dL. CCT now showed clear CVST (superior sagittal/transverse/sigmoid sinuses). Admitted to our Stroke Unit, treatment started with fondaparinux and Igs (PF4-heparinELISA-positve vaccine-induced thrombotic thrombocytopenia, VITT). Seizures were treated with levetiracetam. Because of progressing CVST and addnl. parenchymal bleeding we performed endovascular mech. thrombectomy. Recanalisation was achieved. Platelet-count normalized. Patient recovered. Conclusions Persisting headache after application of COVID-19 vector-based vaccines should be taken seriously even in healthy young women with no apparent vascular risk factors, initially normal platelet-count and unremarkable cerebral imaging. Reevaluation with repeated investigation (examination/laboratory/imaging), if neurol. symptoms persist, might be crucial to detect suspected CVST. Early and extensive therapy with IVIG and endovascular mech. thrombectomy needs further evaluation in these cases.