Background <p>Sepsis is a critical condition with a high mortality rate. Early recognition and appropriate treatment are essential for improving patient outcomes. Biomarkers play an important role in clinical decision-making. There is an increasing interest in biomarker ratios that may better demonstrate the complex interaction between inflammation and host response in sepsis.</p> Objective <p>To compare the prognostic ability of the Platelet/Albumin Ratio (PAR) and the CRP/Albumin Ratio (CAR) in septic patients.</p> Patients and methods <p>The study enrolled 150 critically ill patients diagnosed with sepsis admitted to the department of Critical Care in Cairo university hospital. All patients were subjected to complete history taking, complete physical examination, and full laboratory investigations including complete blood count with differential count, serum level of albumin, C-reactive protein to calculate the PAR and CAR upon admission. Severity scores included APACHE II and SOFA scores were calculated on admission.</p> Results <p>The mortality rate in the study was 28%. CAR demonstrated fair mortality predictive accuracy (<i>P</i> &lt; 0.001), at a cutoff of 40.26, it showed 81% sensitivity and 51.9% specificity. PAR showed poor discriminative ability for predicting mortality with non-significant <i>P</i> value (0.527), However, it showed a significant positive association with both ICU stay (<i>P</i> = 0.008), and hospital stay (<i>P</i> = 0.013).</p> Conclusion <p>CAR is a valuable and cost-effective biomarker ratio that revealed a significantly higher prognostic accuracy than PAR in septic patients.</p>