The medical world has been seeking solutions in solving the Coronavirus disease 2019 (COVID-19) outbreak since 2019. Amongst several alternatives, 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 highlight the unexpected adverse clinical and laboratory outcomes in the majority of COVID-19 patients treated with hemoperfusion in our hospital. We included fifteen patients admitted to the Intensive Care Unit (ICU) with moderate-to-severe 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 improvement 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 evidence, we recommended only performing hemoperfusion for investigational instead of therapeutic purposes due to its poorly understood pathophysiology in COVID-19. We also recommended further research regarding the usage of hemoperfusion in COVID-19 patients, especially in the matter of determining the best time to start the therapy.