Background: In this study, we investigated the ability of end tidal carbon dioxide pressure (PETCO2) to monitor the changes in cardiac output (CO) induced by fluid challenge and to predict fluid responsiveness. Patients and Methods: We conducted our study upon 38 shocked patients requiring fluid challenge (FC). Hemodynamic variables, central venous pressure (CVP), End-tidal CO2, arterial and venous blood gas analysis and cardiac output were recorded before and after fluid challenges. Fluid responders were identified when cardiac output increased more than 15% after fluid challenge, cardiac output (CO) was estimated by measuring left ventricular outflow tract velocity-time integral (LVOT VTI) by transthoracic doppler echocardiography. Results: Twenty-one (55.3%) patients were fluid responders. Fluid challenge induced increase in CO and PETCO2 was moderately correlated (r = 0.5; P 0.002). The area under receiver operating characteristic (ROC) curve of Δ PETCO2 was 0.89±0.05 CI (81- 98) with an increase ≥ 3.13% in PETCO2 can predict fluid responsiveness with 85.7% sensitivity and 88.3% specificity. No other clinical or hemodynamic variables can predict fluid responsiveness. The area under ROC curve of ΔCVP was 0.48±0.1 CI (32- 64) with an increase ≥ 2cmH2O in CVP can predict fluid responsiveness with 38% sensitivity and 76.5% specificity. Conclusions: Our findings indicate that induced changes in PETCO2 during fluid challenge could be used to monitor changes in cardiac output (CO) for prediction of fluid responsiveness in mechanically ventilated shocked patients, under stationary minute ventilation and steady CO2 production