Introduction COVID-19 vaccines have some adverse effects, mostly mild. However, by presenting an immunological challenge to the individual, they could infrequently trigger immune-mediated diseases. Case report We report the case of a 42-year-old woman, with no previous medical history, who received the first dose of vaccine against COVID-19 and developed inflammatory arthralgias, associated with sudden onset dyspnea and hypoxemia. Pulmonary thromboembolism was documented and the diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) was suspected. Autoantibodies were measured confirming this suspicion. After a few days, she presented a massive pericardial effusion with cardiac tamponade that required surgical management. She received treatment with hydroxychloroquine, corticosteroids and anticoagulation with improvement of all symptoms. Discussion There is controversy regarding the potential of COVID-19 vaccines to induce autoimmunity. Studies addressing the safety of using these vaccines have reported the occurrence of mild local and systemic reactions, most frequently in young adults. So far there are few reports of patients who have developed autoimmune or autoinflammatory diseases after getting vaccinated with any of the COVID-19 vaccines. To the best of our knowledge, to date this is one of the first cases of new-onset SLE and secondary APS after COVID-19 vaccination.