The risk of postoperative nausea and vomiting (PONV) is reduced in cigarette smokers by unknown mechanisms. If protection is related to an acute effect of smoke constituents, smokers with the most recent exposure to cigarette smoke would be most protected. We tested the hypothesis that in cigarette smokers, postoperative nausea is correlated with recent exposure to cigarette smoke as quantified by exhaled carbon monoxide (CO) concentrations. In this observational study, exhaled CO levels were measured in 140 female smokers preoperatively. PONV was assessed over the first 24 h after surgery. There was no correlation (assessed with Spearman rank correlation) between preoperative CO and nausea scores at recovery room discharge. Significant correlations were found between nausea assessed over the first 24 h postoperatively and a history of PONV or motion sickness, the use of intraoperative antiemetic prophylaxis, duration of anesthesia, and use of opioids in the postanesthesia care unit. However, there was no correlation between preoperative CO and nausea over the first 24 h. These preliminary data suggest that the effect of smoking in reduced PONV is not directly related to preoperative exhaled CO levels.