Chest X-ray has verified its role as a crucial tool in COVID-19 assessment due to its practicability, especially in emergency units, and Brixia score has proven as a useful tool for COVID-19 pneumonia grading. The aim of our study was to investigate correlations between main laboratory parameters, vaccination status, and Brixia score, as well as to confirm if Brixia score is a significant independent predictor of unfavorable outcome (death) in COVID-19 patients. The study was designed as a cross-sectional multicentric study. It included patients with a diagnosed COVID-19 infection who were hospitalized. This study included a total of 279 patients with a median age of 62 years. The only significant predictor of unfavorable outcome (death) was Brixia score (adjusted odds ratio 1.148,p= 0.022). In addition, the results of the multiple linear regression analysis (R2= 0.334, F = 19.424,p< 0.001) have shown that male gender (B = 0.903,p= 0.046), severe COVID-19 (B = 1.970,p< 0.001), and lactate dehydrogenase (B = 0.002,p< 0.001) were significant positive predictors, while albumin level (B = −0.211,p< 0.001) was a significant negative predictor of Brixia score. Our results provide important information about factors influencing Brixia score and its usefulness in predicting the unfavorable outcome (death) of COVID-19 patients. These findings have clinical relevance, especially in epidemic circumstances.