Preeclampsia (PE) remains a leading cause of maternal and neonatal morbidity and mortality worldwide. Smoking cigarettes is associated with a decreased incidence of PE. Based on this observation and previous work, we hypothesize that women who smoke have a lower risk of developing PE because of elevated levels of carbon monoxide (CO) in their blood. The objective of this study was to determine if low-dose CO in ambient air could attenuate the late pregnancy hypertension (HTN) and proteinuria in the Adenovirus (Ad) sFlt-1 PE-like mouse model. Continuous low-dose CO treatment (250 ppm) was started on E10.5 and maintained until E17.5. Compared to control and Ad empty vector, AdsFlt-1 mice displayed late- gestation HTN (E14.5–17.5) (P<0.05), proteinuria (P<0.05) and reduced Bowman's space which were all prevented with CO treatment. Use of the Ad (with/without sFlt-1) or CO had no effect (p>0.05) on litter size, fetal resorption numbers and fetal or placental weights. This study shows that treatment with CO can prevent HTN and proteinuria in a mouse model of PE. It provides a possible mechanism for the reduced incidence of PE in smoking women, and supports the possibility of using CO as a future treatment for PE.