Objectives: The coronavirus pandemic was associated with a high mortality rate in the Republic of North Macedonia. Finding early markers of the disease’s severity may predict outcomes and guide the treatment of the disease. The aim of our study was to evaluate the role of inflammatory markers in predicting the outcome of COVID-19 in hospitalized patients. Methods: The study included 104 PCR-confirmed COVID-19 patients who underwent hospital treatment at the Institute of Lung Diseases and Tuberculosis in Skopje, North Macedonia, between November 2020 and May 2021. Inflammatory markers were assessed in all patients and correlated with the disease severity and outcome in terms of survival or death. Results: IL-6 and LDH at admission were significantly elevated in patients with a severe or critical form of the disease and among non-survivors. In addition, IL-6 showed 87.9% of sensitivity and 61.8% of specificity for distinguishing non-survivors from survivors with a cut-off value of 21.7 pg/ml in the receiver operator curve (ROC). Procalcitonin was significantly increased in non-survivors. Parallel to the increase of disease severity, the values of CRP and LDH increased significantly during hospitalization. Conclusion: The results of the study indicate that a significant association exists between the highly increased levels of CRP, LDH, IL-6 and procalcitonin and the severity of the disease and mortality in COVID-19 patients. Their measurements and follow-up during the course of the disease could be used as predictors for prognosis and outcome but also as a subject for targeted therapy.