The objective of this report is to systematically review the literature pertaining to the evidence of the relationship between environmental carbon monoxide (CO) and heart rate variability (HRV). For this purpose, reports published in English scientific journals were critically reviewed by the authors employing PRISMA guidelines. Fifteen studies performed in China, Finland, Israel, Mexico, Taiwan, and the USA were identified as eligible to be included in the review. Out of these, 10 studies found a significant relationship between CO and HRV. However, while a proportion of these studies found an increase in parasympathetic tone, other studies found an increase in sympathetic tone. Methodological differences across these studies, including population understudy, sample size, measurement techniques, and accounting for intervening variables do not pave the way for a consensual conclusion. In conclusion, the lack of consistent results on the relationship between CO and HRV as reflected by the present review calls for more research employing appropriate indoor and outdoor ecological designs that account for possible interaction effects and individual differences. Involvement of olfactory receptors is suggested as a possible underlying mechanism for both short response latencies as well as for the diversity between individuals and samples investigated.