Abstract Here we report three clinical cases of children with sickle cell disease (SCD) and severe COVID‐19 who evolved with complications during hospitalization or after discharge. They present single nucleotide polymorphisms in tlr‐7 and tirap genes, identified from 37 patients under 16 years old hospitalized from September 2020 to May 2021 in the Hospital João Paulo II, Belo Horizonte, Brazil. They presented significant complications of SCD as acute chest syndrome, splenic sequestration, and pain crisis during hospitalization or up to 2 months after SARS‐CoV‐2 infection. They all required transfusion of concentrated red blood cells and hospitalization in a reference hospital to care for children with SCD.