Carbon monoxide (CO) is known as a silent killer. In Egypt, it is one of the most common causes of death-related poisonings. This study aimed to evaluate some scoring systems; Glasgow coma scale (GCS), acute physiology and chronic health evaluation II (APACHE II), simplified acute physiology score II (SAPS II) and rapid emergency medicine score (REMS) for predicting in-hospital mortality of patients with acute CO poisoning. One hundred and eight acutely CO poisoned patients were included in the study. For each patient, socio-demographic and toxicological data were recorded. Clinical examination and calculation of the four scoring systems were performed. Patients were divided into two groups; survivors and non-survivors. Discrimination was evaluated using ROC curve and calculating the area under the curve (AUC). The current study revealed that median age of the studied patients was 25.5 years, 55.6% were males and 61.1% were from rural areas. All cases were intoxicated accidently. Among the studied 108 patients; 20 patients died in hospital and 88 patients survived. Both APACHE II and SAPS II had the best AUC, followed by REMS then GCS. The AUC of GCS was significantly lower than those of APACHE II, SAPS II and REMS scores; while differences between AUC of APACHE II, SAPS, and REMS were not statistically significant. It could be concluded that REMS is more useful in predicting in-hospital mortality in acute CO poisoning as it is a simple, easy and rapid scoring system rather than more complicated scoring systems such as APACHE II and SAPS II.