Carbon monoxide (CO) poisoning is one of the most common causes of poisoning death and its diagnosis requires an elevated carboxyhemoglobin (COHb) level. Noninvasive CO saturation by pulse oximetry (SpCO) has been available since 2005 and has the advantage of being portable and easy to use, but its accuracy in determining blood COHb level is controversial. To evaluate the accuracy of SpCO (index test) to estimate COHb (reference test). Systematic review and meta-analysis of diagnostic test accuracy (DTA) studies. Four electronic databases were searched (Medline, Embase, Cochrane Central Register of Controlled Trials, and OpenGrey) on 2 August 2022. All studies of all designs published since the 2000s evaluating the accuracy and reliability of SpCO measurement compared to blood COHb levels in human volunteers or ill patients, including children, were included. The primary outcome was to assess the diagnostic accuracy of SpCO for estimating COHb by blood sampling by modeling receiver operating characteristic (ROC) curves and calculating sensitivity and specificity (primary measures). The secondary measures were to calculate the limits of agreement (LOA) and the mean bias. This systematic review was conducted according to the Preferred Reporting Items for a Systematic Review and Meta-analysis-DTA 2018 guidelines and has been registered on International Prospective Register of Systematic Reviews (CRD42020177940). The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Twenty-one studies were eligible for the systematic review; 11 could be included for the quantitative analysis of the primary measures and 18 for the secondary measures. No publication bias was found. The area under the summary ROC curve was equal to 86%. The mean sensitivity and specificity were 0.77, 95% confidence interval (CI, 0.66-0.85) and 0.83, 95% CI (0.74-0.89), respectively (2089 subjects and 3381 observations). The mean bias was 0.75% and the LOA was -7.08% to 8.57%, 95% CI (-8.89 to 10.38) (2794 subjects and 4646 observations). Noninvasive measurement of COHb (SpCO) using current pulse CO oximeters do not seem to be highly accurate to estimate blood COHb (moderate sensitivity and specificity, large LOA). They should probably not be used to confirm (rule-in) or exclude (rule-out) CO poisoning with certainty.