Various scoring systems and cytokines have been cited as predicting disease severity in COVID-19 infection. This study analyzed the link between mortality rate, levels of cytokines, and scoring systems such as the Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Charlson Comorbidity Index in patients infected with COVID-19. Adult patients infected with COVID-19 were followed up in the intensive care unit (ICU) and analyzed prospectively. We measured serum cytokine levels (Interleukin-10 (IL-10), Interleukin-8 (IL-8), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and High mobility group box 1 (HMGB-1)) and recorded GCS, APACHE II, SOFA, and Charlson comorbidity index scores on admission to the ICU. Receiver operating curve (ROC) analysis was performed to predict mortality from IL-1β, IL-6 IL-10, IL-8, TNF-α, and HMGB-1 values. Study participants were grouped as follows: Group A, survivors, and Group B, deceased, during the 28-day follow-up. The mean age was 65.69 (±13.56) in Group A (n = 36) and 70.85 (±10.06) in Group B (n = 27). The female/male ratio was 23/40. Age, sex, body mass index (BMI), comorbid illnesses, GCS, APACHE II, SOFA, and Charlson scores, duration of hospitalization or ICU admission, therapeutic choices, and lymphocyte, PMNL, NLR, platelet, D-dimer, fibrinogen, GGT, CRP, procalcitonin, and lactate levels were similar between the groups. The frequency of acute kidney injury (AKI) was higher in Group B (p = 0.005). Serum IL-10, IL-8, IL-6, IL-1β, TNF-α, HMGB-1, ferritin, and LDH values were higher, and PaO2/FiO2 was lower in Group B than in Group A. ROC analysis showed that there was an association between serum IL-1β (>1015.7), serum IL-6 (>116.7), serum IL-8 (>258.4), serum IL-10 (>247.5), serum TNF-α (>280.7), and serum HMGB-1 (>23.5) and mortality. AKI gave rise to a greater risk of mortality (odds ratio: 7.081, p = 0.014). Mortality was associated with serum IL-10, IL-8, IL-6, IL-1β, TNF-α, and HMGB-1 but not with GCS, APACHE II, SOFA, or Charlson comorbidity index scores. AKI increased the risk of mortality by seven times. Our findings suggest that cytokine levels (serum IL-10, IL-8, IL-6, IL-1β, TNF-α, and HMGB-1) were predictors of mortality in COVID-19 infection. In addition, our results might give an opinion about the course of COVID-19 infection.