Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolytic anemia, bone marrow failure, thrombophilia. COVID-19, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with many variants including Omicron. This study depicted demographic and clinical characteristics of 20 PNH patients with SARS-Cov2 Omicron infection. All the patients hadn’t previously been administrated with complement inhibitors. They all were with high disease activity (HDA), and LDH level exceeded any documented since the diagnosis of PNH, and those reported in the literature for previously stable treatment with complement inhibitors. D-dimer level elevated in 10 patients. 2 patients developed mild pulmonary artery hypertension. Glomerular filtration rate (GFR) declined in 5 patients. 1 patient developed acute renal failure and underwent hemodialysis. Anemia and hemolysis were improved in 5 patients treated with eculizumab. Hemolytic exacerbation of PNH with COVID-19 is severe and eculizumab may be an effective treatment.