Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus has become a worldwide pandemic since first discovered in 2019. Systemic lupus erythematosus (SLE) flare has been reported in the post‐infectious period. In Colombia, the fourth pandemic wave started at the beginning of 2022 when we observed flare of 3 SLE patients during active infection. Case presentation We describe 3 patients with inactive SLE, who presented coronavirus disease 2019 and severe flare in early 2022, 2 patients with nephritis and 1 with severe thrombocytopenia. All patients had increase of antinuclear and anti‐DNA antibody titers and complement consumption. Conclusions Three cases with SLE flare concomitant with active SARS‐CoV‐2 infection were different from others reported earlier in the pandemic with post‐infectious flare.