The medical world has been seeking solutions in solving the Coronavirus disease 2019 (COVID-19) outbreak since 2019. Amongst several alter-natives, hemoperfusion therapy has been reported to be beneficial for alleviating symptoms and reducing mortality in severely ill COVID-19 patients. Hemoperfusion is a process of filtering blood to eliminate toxins and inflammatory factors from the body. This case series aims to high-light the unexpected adverse clinical and labora-tory outcomes in the majority of COVID-19 patients treated with hemoperfusion in our hospi-tal. We included fifteen patients admitted to the Intensive Care Unit (ICU) with moderate-to-se-vere COVID-19 between August and December 2020 and were all given two to four sessions of hemoperfusion using the MG150® cartridge. All ten men and five women showed no improve-ment in their neutrophil-lymphocyte ratio (NLR), ferritin, D-dimer, and C-reactive protein (CRP) values after the hemoperfusion regiments, both survivors and non-survivors. In addition, eleven out of twelve patients with respiratory failure who were then intubated resulted in death. Based on our findings and previous evi-dence, we recommended only performing hemoperfusion for investigational instead of therapeutic purposes due to its poorly under-stood pathophysiology in COVID-19. We also recommended further research regarding the us-age of hemoperfusion in COVID-19 patients, es-pecially in the matter of determining the best time to start the therapy. © 2023, The Indonesian Foundation of Critical Care Medicine. All rights reserved.