The evidence supporting additional hemoperfusion (HP) with cytokine adsorbents for improving clinical outcomes in severe to critical coronavirus disease 2019 (COVID-19) patients remains limited. We compared severe to critical COVID-19 patients who received additional HP with a cytokine adsorbent to matched cases receiving standard medical treatment (SMT). The primary outcome was hospital mortality. In our study, we matched 45 patients who received additional HP 1:1 with the SMT group based on key clinical parameters. The hospital mortality rates did not differ between the groups (33% vs 38%, p = 0.83). The HP group had a significantly shorter ICU stay (22 vs 32 days; p = 0.017) and reduced mechanical ventilation duration (15 vs 35 days; p < 0.001). Additionally, the incidence of pulmonary complications (20% vs 42%; p = 0.04), sepsis (38% vs 64%; p = 0.02), and disseminated intravascular coagulopathy (DIC) (13% vs 33%; p = 0.046) were significantly lower in the HP group. In conclusion, among severe to critical COVID-19 patients, additional HP with a cytokine adsorbent did not improve hospital mortality. However, it reduced ICU length of stay, mechanical ventilator days, and incidences of lung complications, sepsis, and DIC.Trial registration: TCTR20231002006. Registered 02 October 2023 (retrospectively registered).