The effects of environmental tobacco smoke (ETS) are less studied especially on neonates. This study evaluates the clinical and biochemical effects in neonates exposed to ETS during pregnancy. Two hundred pregnant women asked to complete the questioners about their ETS. Ninety from them were enrolled in biochemical assays as two groups according to ETS. The cotinine level determined in saliva and serum of mothers to confirm their tobacco exposure. The routine tracheal suction from the fetus was used to determine the level of neuron specific enolase (NSE), soluble E-cadherin, sApo-1/Fas, nitric oxide (NO) and cotinine. In clinical assessment, the percent of full term babies in nonexposed group (72 %) are higher compared to exposed group (67 %). Apgar score at the first min, admission to intensive care unit (ICU) and morbidity during the first month shows statistical significance increase in exposed compared to non-exposed group (p = 0.03, 0.05, 0.01, respectively). The new born weight in exposed group significantly decreased compared to non-exposed group (2,850 g ± 3.74 vs 2,967.67 g ± 3.34; p = 0.02). In biochemical assessment, NSE and sE-cadherin significantly increased, while NO significantly decreased (p = 0.000) in exposed compared to non-exposed group. There is a positive correlation between level of cotinine and both NSE, sE-cadherin (r = 0.7, 0.9; p = 0.000, 0.006, respectively). To our knowledge, this is the first study link between prenatal tobacco exposure (PTE) and biochemical parameters measured in tracheal suction. PTE will lead to decrease in birth weight most probably by decreasing NO, sFas, and increasing sE-cadherin. While, increased morbidity of neonates in the exposed group could be attributed to cessation of breast feeding and its complication and increased NSE in the studied markers.