The development of organ dysfunction is a key contributor to morbidity and mortality in sepsis. End-tidal carbon dioxide levels measured by non-invasive end-tidal capnography (ETCO2) may provide a rapid assessment of a patient's underlying metabolic status. The objective of this study was to explore the association between ETCO2 and (1) organ dysfunction [sequential organ failure assessment (SOFA) score], and (2) serum lactate levels in febrile emergency department (ED) patients. Prospective, observational cohort study of a convenience sample of 97 adult (age 18 years or older) patients presented to an academic urban ED with a fever and suspected infection. The outcomes were ED SOFA score and serum lactate level. Based on prior studies, we categorized an ETCO2 <35 mmHg, a priori, as abnormal for the exposure. We defined clinically significant organ failure as a SOFA score of >2, and an abnormal lactate as >4 mmol/L. The correlation of ETCO2 with SOFA and lactate level was analyzed using Pearson correlation coefficient. Operating characteristics were calculated with 95% confidence intervals, along with the area under the curve (AUC). Among 97 patients enrolled, 5 (5%) had an abnormal lactate and 34 (35%) had a SOFA score >2. A significant correlation was found between ETCO2 and SOFA score (r = -0.35, p < 0.01), and ETCO2 and lactate level (r = -0.35, p < 0.01). A receiver operator curve for ETCO2 and SOFA >2 had an AUC of 0.69. ETCO2 of <35 has a sensitivity of 0.73 (95% CI 0.56-0.85) and specificity 0.50 (0.38-0.62) in predicting SOFA scores >2. ETCO2 <35 has a sensitivity of 0.60 (0.22-0.88) and specificity 0.42 (0.32-0.52) in predicting lactate >4 with an AUC of 0.62. We found a small, but statistically significant correlation, between ETCO2 and SOFA scores; however, based on questionable operating characteristics, the test seems to have limited ability to meaningfully impact clinical decision making. Larger confirmatory studies are required before final assessment.