Background: Maternal smoking exposure during pregnancy is correlated with negative neonatal well-being due to placental disruption. Currently, there are still conflicting findings on whether smoking affects neonatal inflammatory responses. This study aimed to evaluate the effects of maternal smoking exposure on neonatal wellbeing. Materials and Methods: This is a cross-sectional study. Pregnant subjects were grouped into three categories: active smokers, passive smokers, and non-smokers. Smoke analyzer was used to measure levels of exhaled carbon monoxide (CO), and the levels of tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), and cotinine in serum umbilical cord were measured by enzyme-linked immunosorbent assay (ELISA). The newborn well-being such as birthweight, birth length, and head circumference was also measured. Statistical analysis was performed using IBM SPSS version 25. Results: A total of 85 pregnant subjects participated in this study, distributed as 20 active smokers (23.5%), 35 passive smokers (41.2%), and 30 non-smokers (35.3%). Newborns’ weight and placental weight had significant differences between each maternal group. IFN-γ and TNF-α in the groups exposed to cigarettes were lower compared to the non-smoker group. Exhaled CO and cotinine cord blood levels were associated with smoking. Serum cord blood TNF-α levels inversely correlated with exhaled CO but were not significant. Conclusions: Maternal smoking exposure was associated with alteration of neonatal well-being and inflammatory markers. © 2025, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.