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SARS-CoV-2 infection is associated with an increased rate of thromboembolic events and mortality. Different vaccines are globally used to limit the pandemic. In this report, we present the case of two young female patients with newly diagnosed cerebral sinus vein thrombosis occurring after injection of the vector-based ChAdOx1 vaccine. Both patients presented with unusual headache only. The two of them used an estrogen-containing contraception, had had a history of deep venous thrombosis, and both had MTHFR mutations. Both patients developed SARS-CoV-2 specific humoral and cellular immunity including both CD4 and CD8 T cells. This rare, but serious complication needs to be considered after vaccination of young females, even if there is no evidence of heparin-induced thrombocytopenia., (© 2021. The Author(s).)