SARS-CoV-2 causes a hypercoagulable state that predisposes patients to thromboembolic events. We report two adolescents with Sickle Cell Disease (SCD) who developed pulmonary embolism (PE) during acute chest syndrome (ACS) episode associated with a possible SARS-CoV-2 infection. Both SCD and SARS-CoV-2 infection predisposes to thromboembolic disease. Thromboprophylaxis with LMWH should be considered in adolescent with ACS, related or not to COVID-19 disease.