Introduction: Sepsis associated with ventilator-associated pneumonia (VAP) causes mortality in intensive care unit (ICU) patients. The time of diagnosis is crucial, and microbiological cultures take time. In this study, the diagnostic accuracy of CD64 index to predict VAP-induced sepsis and survival time in subjects requiring mechanical ventilation were evaluated and compared to conventional biomarkers and culturing methods. Methodology: A total of 32 subjects with VAP were included. Sepsis after VAP was diagnosed in 25 (78.1%) patients according to clinical signs, radiographic examination, and samples of blood and trachea taken for culturing. Simultaneously with cultures, CD64 index on neutrophils, C-reactive protein (CRP), procalcitonin (PCT), and count of leucocytes and neutrophils were determined. Results: Biomarker values were evaluated in both groups of subjects (with and without sepsis after VAP). The values of CD64 index and CRP were significantly higher in the sepsis group. Receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.929 for CD64 index in differentiating subjects with VAP-induced sepsis from those without sepsis. The biomarkers CRP and PCT showed comparable results (AUC of 0.869 and 0.909, respectively). Blood cultures were positive in 12 subjects, endotracheal aspirate in 19. CD64 index and isolation of pathogen with positive blood cultures or from endotracheal aspirate (positive in 24 cases) could predict survival time before application of more targeted antibiotic therapy. Conclusions: CD64 index may be used as a useful diagnostic tool to recognize VAP-induced sepsis; moreover, accompanied with an identified pathogen, can predict survival for ICU patients.