Background: Micronutrient deficiencies and excesses may indeed contribute to bipolar disorder (BD) and major depressive disorder (MDD). Objectives: This study aimed to compare the concentrations of copper (Cu) and zinc (Zn) in patients with BD and MDD, as well as to determine the relationship between trace element levels and the profile of affective disorders as biomarkers for the disease. Patients and Methods: This case-control study was conducted on 135 patients between the ages of 18 and 40, both sexes, who met the DSM-V diagnostic criteria for BD and MDD (regardless of the stage of the illness). Patients were divided into three equal groups. Group A had MDD; group B had BD, while group C was a healthy control individual. Results: Groups A and B exhibited significantly higher Cu levels compared to group C (P <0.001). Zinc levels were significantly lower in groups A and B compared to group C (P <0.05). The levels of Cu and Zn were similar in both the A and B groups. No correlation was found between serum levels of Cu and Zn and the onset of disease or age. A positive correlation was found between serum Cu levels and (disease severity and YMRS score) (p < 0.05), while a negative correlation was identified between serum Zn levels and (illness severity and YMRS score) (p < 0.05) and between serum Cu and Zn (P=0.010). Conclusion: MDD and BD are associated with higher serum Cu levels and lower serum Zn.