question: BACKGROUND/AIM: It is claimed that aberrant immune response has a more important role than the cytopathic effect of the virus in the morbidity and mortality of the coronavirus disease 2019 (COVID-19). We aimed to investigate the possible roles of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway and leukotrienes (LT) in uncontrolled immune response that occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MATERIALS AND METHODS: This study included 25 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed-tomography. Serum TWEAK, LTE4, and prostaglandin F2α (PGF2α) levels were determined. RESULTS: Compared with the healthy control group, TWEAK, LTE4, and PGF2α levels were higher in the group of SARS-CoV-2 infection without lung involvement. In the group of SARS-CoV-2 infection with lung involvement, age, fibrinogen, sedimentation, C-reactive protein and ferritin, TWEAK, LTE4, and PGF2α levels were higher, and lymphocyte levels were lower compared with the asymptomatic group. CONCLUSIONS: In the study, TWEAK and LTE4 levels increased in cases with COVID-19. These results support that TWEAK/Fn14 pathway and LT may involved in the pathology of aberrant immune response against SARS-CoV-2. Inhibition of each of these pathways may be a potential target in the treatment of COVID-19.