Objective: This study aims to compare the effectiveness of non-invasive pressure of transcutaneous CO2 (PtcCO(2)) and O-2 (PtcO(2)) analyzers versus conventional blood gas sampling in patients with sepsis and septic shock. Materials and Methods: Sepsis patients without a need for inotrope support (sepsis) were prospectively enrolled to group 1 (n=50), whereas group 2 (n=50) was composed of patients needing inotropes (septic shock). Demographic data, laboratory tests, Acute Physiology and Chronic Health Evaluation-II (APACHE-II) and Sequential Organ Failure Assessment (SOFA) scores, standard monitoring data, data of blood gas analysis (pH, PaCO2, PaO2, and SaO(2)), and transcutaneous CO2 and O-2 were collected at the first, second, third, and fourth hours. Results: No significant difference was noted between the groups in terms of demographic parameters, baseline white blood cell, hematocrit, baseline heart rate, central venous pressure, respiratory rate, and positive end-expiratory pressure values. Group 2 had significantly higher serum urea and creatinine levels and lower albumin levels and mean arterial pressure, whereas group 1 had significantly lower APACHE-II and SOFA scores and peak inspiratory pressure and FiO(2). No significant difference was noted between the PtcCO(2) and PaCO2 values in group 1, whereas the PtcCO(2) values of group 2 were significantly lower than PaCO2. PtcO(2) and PaO2 values were significantly lower in group 1, whereas PtcO(2) vs PaO2 values were significantly lower in group 2. A strong correlation was noted between arterial and transcutaneous CO2 and O-2 values in both the groups. Conclusion: PtcCO(2) assessment may be an alternative method in patients with sepsis but not in septic shock. PtcO(2) measurement may not be a reliable method for patients with sepsis and septic shock.