(1) Background: Since its discovery, COVID-19 has caused more than 256 million cases, with a cumulative death toll of more than 5.1 million, worldwide. Early identification of patients at high risk of mortality is of great importance in saving the lives of COVID-19 patients. The study aims to assess the utility of various inflammatory markers in predicting mortality among hospitalized patients with COVID-19. (2) Methods: A retrospective observational study was conducted among 108 patients with laboratory-confirmed COVID-19 hospitalized between 1 May 2021 and 31 October 2021 at Municipal Emergency Clinical Hospital of Timisoara, Romania. Blood cell counts at admission were used to obtain NLR, dNLR, MLR, PLR, SII, and SIRI. The association of inflammatory index and mortality was assessed via Kaplan–Maier curves univariate Cox regression and binominal logistic regression. (3) Results: The median age was 63.31 ± 14.83, the rate of in-hospital death being 15.7%. The optimal cutoff for NLR, dNLR, MLR, and SIRI was 9.1, 9.6, 0.69, and 2.2. AUC for PLR and SII had no statistically significant discriminatory value. The binary logistic regression identified elevated NLR (aOR = 4.14), dNLR (aOR = 14.09), and MLR (aOR = 3.29), as independent factors for poor clinical outcome of COVID-19. (4) Conclusions: NLR, dNLR, MLR have significant predictive value in COVID-19 mortality.