ABSTRACT: Critically ill COVID-19 patients with pleural effusion experience longer hospitalization, multisystem inflammatory syndrome, and higher rates of mortality. Generally, pleural effusion can serve as a diagnostic value to differentiate cytokine levels. This study aimed to evaluate the pleural effusions of COVID-19 deceased patients for 182 protein markers. Olink® Inflammation and Organ Damage panels were used to determine the level of 184 protein markers, e.g., ADA, BTC, CA12, CAPG, CD40, CDCP1, CXCL9, ENTPD2, Flt3L, IL-6, IL-8, LRP1, OSM, PD-L1, PTN, STX8, and VEGFA, which were raised significantly in COVID-19 deceased patients, showing over-stimulation of the immune system and ravaging cytokine storm. The rises of DPP6 and EDIL3 also indicate damage caused to arterial and cardiov