Objective: To determine levels of trace elements [copper (Cu), zinc (Zn), selenium (Se), and cobalt (Co)] and heavy metals [arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd)] in the plasma of mothers and infants and investigate the relationship between those levels and neural tube defects (NTD). Methods: A total of 100 neonates diagnosed with NTD and placed in the Neonatal Intensive Care Unit of Yuzuncu Yil University, Turkey between May 2013 and December 2016 comprised the study group. The control group consisted of 70 healthy neonates not diagnosed with NTD or any other congenital anomalies. For both the groups, mother and infant plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and compared. Plasma levels of Cu, Zn, Co, Cd, Se, Hg, As, and Pb were measured and compared between two groups of mothers and infants. Findings: Mother and infant plasma levels of trace elements Zn and Se were determined to be significantly lower in the study group compared with the control group, while Cu levels were significant elevated in the study group (all p values < .05). Plasma levels of heavy metals As, Pb, and Cd were found to be significantly higher in the NTD control group (p < .05 for all). There was no association between maternal infection, maternal smoking status, history of miscarriage, or history of NTD with the development of NTD (p > .05). Differences in maternal age, birth weight, length of gestation, and infant gender for the two groups were also determined not to be statistically significant. Results: High plasma levels of heavy metals As, Pb, and Cd and trace element Cu were identified as risk factors for the development of NTD. At the same time, low plasma levels of trace elements Zn and Se were also found to be risk factors for NTD. However, no association between Hg and Co plasma levels and increased risk for the development of NTD was observed. This study, while being the most comprehensive case study to date investigating the relationship between heavy metals and trace element levels and increased risk of NTD, nonetheless highlights the need for further research in order to make definite statements regarding this relationship.