Background: Sepsis is a complex condition defined by the systemic response to infection. Severity assessment scoring systems are used to aid the physician in deciding whether aggressive treatment is needed or not. In this study, two severity assessment scoring systems, namely Acute Physiology and Chronic Health Evaluation II (APACHE II) and CURB-65 were compared to assess their sensitivity and specificity. Aim of Study:To compare the efficacy between CURB-65 and APACHE II in assessment of the severity of sepsis and predicting mortality in critically ill geriatric patients.Patients and Methods: This prospective comparative study was conducted on patients admitted at Critical Care department of Ain Shams University Hospitals, Cairo, Egypt, for 3 months duration. Patients admitted to the general ICU of Ain Shams University Hospitals with sepsis or septic shock of both sexes Results: The simplicity of calculation of CURB65 demonstrated superiority over other complex severity scores utilized in crowded emergency rooms. Furthermore, the CRB65 score, which does not require a blood urea level, is more suitable for use in gross-roots hospitals. In the current study, CURB-65 score was statistically significantly higher in the non-survivors as compared with the survivors (1.79 ± 1.26 and 0.65±0.43 respectively) (p<0.001). Moreover, in our study, the cutoff point of Curb-65 score to differentiate between non-survivors from survivors was >2 with 59% sensitivity and 92.3% specificity. Unfortunately, no much data is available to describe the prognostic ability of CURB65 in patients with sepsis, as the score was originally developed to assess the prognosis in pneumonia patients. Conclusion:Sepsis is a life threating condition and is one of the leading causes of death. Mortality was reported in 55.7% of patients by the end of the study period. APACHE II was predicting mortality with 84.6% sensitivity and 64.5% specificity, 78.8% PPV & 86.4% NPV and 82.2% accuracy. The length of hospital stay was significantly longer in nonsurvivor group. CURB-65 was statically significantly higher in the non-survivors as compared with the survivors with 59% sensitivity and 92.3% specificity but no much data available to describe prognostic ability of CURB-65 in-patient with sepsis as in pneumonia patients.